The following is a recent review of the literature regarding marijuana.  Printed in the J. Am. Board Fam. Med., and copied in Medscape, it describes the medical uses of marijuana and its derivatives, and reviews the medical-legal aspects of this drug's usage.

www.medscape.com

Cannabis and Its Derivatives

Lawrence Leung, MBBChir, MFM(Clin)

 

Posted: 08/30/2011; J Am Board Fam Med. 2011;24(4):452-462. © 2011 American Board of Family Medicine

Abstract and Introduction

Abstract

Background: Use of cannabis is often an under-reported activity in our society. Despite legal restriction, cannabis is often used to relieve chronic and neuropathic pain, and it carries psychotropic and physical adverse effects with a propensity for addiction. This article aims to update the current knowledge and evidence of using cannabis and its derivatives with a view to the sociolegal context and perspectives for future research.
Methods: Cannabis use can be traced back to ancient cultures and still continues in our present society despite legal curtailment. The active ingredient, Δ9-tetrahydrocannabinol, accounts for both the physical and psychotropic effects of cannabis. Though clinical trials demonstrate benefits in alleviating chronic and neuropathic pain, there is also significant potential physical and psychotropic side-effects of cannabis. Recent laboratory data highlight synergistic interactions between cannabinoid and opioid receptors, with potential reduction of drug-seeking behavior and opiate sparing effects. Legal rulings also have changed in certain American states, which may lead to wider use of cannabis among eligible persons.
Conclusions: Family physicians need to be cognizant of such changing landscapes with a practical knowledge on the pros and cons of medical marijuana, the legal implications of its use, and possible developments in the future.

Case 1

Scenario

You are a family physician in Ontario, Canada. A 54-year-old man suffering from multiple sclerosis came to your office asking for a prescription for medical marijuana to control his pain. He was taking continuous-release morphine, gabapentin, and lamotrigine, but this combination was still insufficient. He visited Florida a few times, where he smoked cannabis, which helped tremendously to reduce the neuropathic pain and detach his mind from it. He would like to continue using cannabis but is worried about the legal implications and the purity of sample he may obtain on the street.

Suggested Management

The evidence of various forms of cannabis (smoked, oral, and oromucosal spray) for treating neuropathic pain caused by multiple sclerosis should be discussed against the known harms and challenges of usage. Sativex (legally available form of cannabis in Canada; GW Pharmaceuticals, Salisbury, Wiltshire, UK) could be recommended as a first-line treatment. If the patient still decided to pursue a smoked or oral extract of cannabis, referral should be made to recognized specialists in Quebec for a full assessment of eligibility of patient's use and possession of medical marijuana. Close monitoring of the patient would be necessary.

Case 2

Scenario

You are a family physician in the state of California. A 65-year-old male veteran came to your office as a new patient. He had a history of chronic leg pain caused by a shrapnel injury he suffered during the Vietnam War in 1968. Since the 1970s, he has been treated at the local veterans hospital under a pain management program, but control has been unsatisfactory. When asked if he used any recreational drugs, including marijuana, he evaded your question and said he needed to stay on the pain program. You suspected he was using marijuana for his chronic pain.

Suggested Management

The patient should be informed of the new directive from the Veterans Health Administration regarding veterans' use of marijuana and be reassured that he would not be denied his pain management services at the veterans hospital on that basis. He also should be encouraged to discuss his marijuana use with you so that you can monitor his progress. Liaising with an addiction medicine specialist can be helpful to ensure the best follow-up of this patient.

Cannabis, also known as marijuana, refers to the preparation 53 from the plant belonging to the family Cannabaceae, the genusCannabis, and the species Cannabis sativa, which possess psychoactive effects. The flowering tops, leaves, and stalks of the mature female plant are commonly used as the herbal form of cannabis, but sometimes the resinous extract of compressed herb is also used and is called "hash." Archaeologists have identified fibers from cannabis stems in specimens dating back to 4000 BC, and its incorporation into textiles and paper was found in the tombs of the Chinese Han dynasty (~100 BC).^[1] The first record of cannabis as a medicine can be found in the oldest Chinese pharmacopeia, Shen Nong Ben Cao Jing, written in the Eastern Han Dynasty (AD 25 to AD 220), which was indicated for rheumatic pain, malaria, constipation, and disorders of the female reproductive system.^[2] Though the cannabis leaf and stem is rarely used nowadays in Chinese herbal medicine, cannabis seeds, which contain very few psychoactive ingredients, are still commonly prescribed for their laxative effects.^[2]Smoking cannabis is often an under-reported behavior in our society, with a reported prevalence from the World Health Organization of 3.9% among the global population aged 15 to 64 years.^[3] There are more than 70 psychoactive compounds called "cannabinoids" that have been identified in cannabis,^[4] among which Δ9- tetrahydrocannabinol (THC) accounts for most of the psychological and physical effects, and its content is often used as a measure of sample potency. We now know that THC acts on 2 types of cannabinoid receptors: CB₁ and CB₂. CB₁ receptors are mainly found in the brain, peripheral nerves, and autonomic nervous system,^[5] whereas CB₂ receptors are found both in the neurons and immune cells.^[6] THC exerts its effects primarily via CB₁ receptors.

The Laws Regarding Cannabis

In the United States, cannabis is an illicit drug either to possess or trade. Since the inception of the Controlled Substance Act in 1970, the US Federal Law penalizes any act of possessing, dispensing, and prescribing marijuana. Enforcement of prohibition carries an annual price tag of up to $7.7 billion in the United States alone.^[7] However, since 1996 the situation has been changing rapidly—14 states (California, Alaska, Oregon, Washington, Maine, Hawaii, Colorado, Nevada, Vermont, Montana, Rhode Island, New Mexico, Michigan, and New Jersey) already have amended their state laws to allow the use of marijuana by persons with debilitating medical conditions as certified by licensed physicians.^[8,9] The impact has been significant: a recent study in Washington estimated that per annum, up to 2000 licensed physicians have prescribed medical cannabis;^[10] in California, more than 350,000 patients already possess a physician's recommendation to use cannabis.^[11] Nevertheless, among these 14 states, there is substantial variation in the regulation of the quality control, prescription limit, patient registry, and dispensing outlets. For example, in Oregon and Washington, it is legal to possess up to 24 ounces of marijuana, but in Nevada, Montana, and Alaska, the legal limit is only 1 ounce.^[8] Cannabis is currently schedule I; additional research would be facilitated if the drug were reclassified to schedule II.^[8] From a public health standpoint, there is some evidence that decriminalization of cannabis could free up law enforcement resources to curtail other trafficking activities without leading to increased cannabis abuses.^[12] Overall, however, the US Federal law remains unchanged regarding the penal stance toward marijuana, creating various ambiguities and difficulties. For those veterans who are permitted to use medical marijuana by law of their state, these difficulties have been lessened. This has posed an administrative dilemma for those veterans who are allowed to use; the Department of Veterans Affairs issued a directive in July 2010 that permits veterans to continue their use of medical marijuana in states where it is legal without losing their medical benefits from Veterans Affairs.^[13]

Recent news from USA Today ^[14] reports that the US federal government has issued warning letters to several states that have approved the use of medical marijuana with an implication that anyone involved in the growth, operation, or legal regulation of medical marijuana will be subjected to prosecution. These states include Washington, California, Montana, and Rode Island. This was coupled by recent large-scale raids at marijuana growing operations in Montana. Despite reassurance from Eric Holder, US Attorney General, that the penal policy is directed at those who violate both deferral and state laws, this unexpected siren from the federal government has been heard loud and clear, leading Governor Chris Gregoire, of the state of Washington, to abort a proposal to create licensed marijuana dispensaries and Governor Chris Christie, of the state of New Jersey, to postpone plans for marijuana operators.

In Canada, it is also illegal to trade or possess 104 marijuana according to provincial and government laws. However, access to marijuana for medical use is possible under Health Canada's Marijuana Medical Access Regulations, which came into force on July 30, 2001.^[14] The regulations clearly outline 2 categories of persons who can apply to possess for an authorization to possess marijuana for medical purposes. Category 1 refers to people with end-of-life care; seizures from epilepsy; severe pain and/or persistent muscle spasms caused by multiple sclerosis, spinal cord diseases, or spinal cord injury; severe pain; cachexia; anorexia; weight loss and/or severe nausea from cancer or HIV/AIDS infection. A medical declaration from a licensed medical practitioner is required. Category 2 refers to people who have debilitating symptom(s) of medical condition(s), other than those described in category 1, which have failed conventional medical treatment. An assessment by a designated specialist is necessary along with a medical declaration from a licensed medical practitioner.

Under the regulations, the maximum amount of marijuana that can be possessed by any authorized user is a 30-day total of daily requirement. Health Canada sources its supply of dried marijuana and seeds from Prairie Plant Systems Incorporated (Saskatoon, Saskatchewan, Canada), a company that specializes in the growing, harvesting, and processing of plants for pharmaceutical products and research. Alternatively, authorized marijuana users can apply for a permit to produce and grow their own supply provided they meet specific and detailed criteria.

The Harms of Cannabis

Physical and Psychiatric Effects

Among naive users, cannabis smoking often leads to adverse effects. Physical symptoms include increased heart rate and fluctuations in blood pressure;^[15] psychomotor sequelae include euphoria, anxiety, psychomotor retardation, and impairment of cognition and memory.^[16] The estimated lethal dose for humans is between 15 g and 70 g.^[3] When compared with cigarette smoke, cannabis contains a similar array of detrimental and carcinogenic compounds, some of which are present even at higher concentrations.^[17] Among chronic users, population studies have associated cannabis use with decreased pulmonary function, chronic obstructive airway diseases, and pulmonary infections,^[18] although data may be confounded by concomitant tobacco smoking and other social factors. In vitro and in vivo animal studies have demonstrated mutagenic effects of cannabis smoke, and precancerous pulmonary pathology as seen in tobacco smokers has been described in cannabis users.^[19] Nevertheless, there is still inconsistency from the published literature regarding an increased risk for upper respiratory tract cancer caused by cannabis smoking.^[3,18] Various reports have associated cannabis with cardiac arrhythmias,^[20,21] coronary insufficiency^[22–24]and myocardial infarction.^[25,26] A retrospective cross-sectional study revealed a 4.8-times increased risk of developing myocardial infarction within the first hour after smoking cannabis. Earlier data from population studies^[27,28] and meta-analysis^[29] have associated cannabis smoking with low birth weight,^[29] which is maybe confounded by cigarette smoking and socioeconomic status and is not supported by more recent studies.^[30,31] Finally, the controversial link of cannabis use and psychosis has found more support in recent publications.^[32–34]

Dependence and Abuse

Cannabis is recognized as a substance with a high potential for dependence, which occurs in 1 out of 10 people who have ever used cannabis. It leads to behaviors of preoccupation, compulsion, reinforcement, and withdrawal after chronic use.^[35] An Australian survey found that symptoms of cannabis withdrawal satisfied the diagnostic criteria of both International Classification of Diseases 10 and Diagnostic and Statistical Manual of Mental Disorders IV for substance dependence, which included sleep disturbance, anorexia, irritability, dysphoria, lethargy, and cravings.^[36] In the United States, cannabis is now ranked among alcohol and tobacco as one of the most common substances of among adolescents.^[37] There is also ample evidence indicating that regular use of cannabis predicts subsequent psychosocial problems and abuse behavior of other addictive substances. A review of cohort studies by McLaren et al^[38] supported a causal link between cannabis use and psychosis. A recent 10-year follow-up study of adolescents in Australia who used cannabis occasionally were found to be at higher risks of drug abuse and educational problems.^[39] However, several issues have been identified in the published literature about cannabis, which have limited our understanding on the adverse effects of cannabis: (1) lack of consensus on the definition and classification of different types of cannabis users (heavy, regular, occasional, and nonusers); (2) variable quality of studies regarding design, effect sizes, and control of confounding factors; and (3) the polarization of the approach to either studying nonusers versus light/infrequent users or, infrequent/light/nondependent users versus frequent/heavy/dependent users.^[40]

New Kids on the Block

Recently, synthetic analogues of marijuana, known generically as "spice" or "K2," have gained rapid popularity among youths in the Unites States and Europe. Marketed as an incense or herbal blend, the exact constituents of spice has been a myth, and its place of origin is often unclear. Despite sharing similar psychotropic effects as genuine cannabis, spice cannot be reliably tested by drug screens and poses a technical problem for the law enforcement; hence it is capable of evading legal scrutiny among most states in America. A report from the Drug Enforcement Administration of the US Department of Justice in June 2010 had divulged the possible constituents of spice (or K2), which included HU-210, JWH-018, JWH-073 and CP-47,497,^[41] all of which were synthetic cannabinoids legally endorsed for scientific research. This was echoed by a recent research publication that identified a synthetic cannabinoid in commercially obtained spice, JWH-018, which activated CB₁.^[42]

Analgesic Potential and Synergism With Opioids

Despite legal curtailment, cannabis is still used by 10% to 15% of patients with multiple sclerosis^[43] and noncancer types of chronic pain^[44] for both analgesia and psychological detachment. Various well-designed, randomized, placebo-controlled trials have shown that smoked cannabis can relieve peripheral,^[45] posttraumatic,^[46] and HIV-induced^[47,48] neuropathic pain. Evidence has been accumulating from molecular and cell-signaling studies that suggest that the opioids and cannabinoid systems can interact synergistically to enhance analgesic effects.^[49] Animal studies have shown that topical cannabinoid enhances the action of topical morphine,^[50] an effect that is preserved in a morphine-tolerant state.^[51] Moreover, cannabinoids are increasingly being recognized in animal models for their potential sparing effects with opioids^[52] of neuropathic pain and arthritic pain.^[53] Although similar effects have not been translated to human studies, Robert et al^[54] found a synergistic affective analgesia between Δ9-THC and morphine in experimentally induced pain in human volunteers.

Evidence From Clinical Studies

To review the latest evidence of cannabis use and its derivatives, a literature search was conducted from the MEDLINE, EMBASE, PsycINFO, and Cochrane Database of Systematic Reviews from their inception dates to 30 November 2010, using the following keywords: "cannabis," "marijuana," "Δ9-tetrahydrocannabinol," "clinical trial," "benefits," and "side effects." Relevant articles were selected and their quality of evidence was rated according to the Strength of Recommendations Taxonomy (SORT),^[56] with recommendations rated as A, B, or C. The results are summarized in Table 1. In brief, the efficacy of smoked cannabis has been studied for Gilles de la Tourette syndrome, glaucoma, and pain, with good evidence for clinical benefits in HIV-induced neuropathic pain. Oral extract of cannabis has better evidence of relieving self-reported symptoms of spasticity caused by multiple sclerosis. Finally, the oromucosal form of cannabis extract (Sativex, GW Pharmaceuticals) is efficacious for peripheral and central neuropathic pain, especially that caused by multiple sclerosis.

Table 1. Clinical Studies of Cannabis and Its Derivatives with SORT Level of Recommendation⁵⁶

Agent	Condition Indicated	Form of delivery	Nature of Study	Patients (n)	Outcome Measures	Outcome	SORT Level of Recommendation	Reference
Cannabis	Gilles de la Tourette Syndrome	Smoking	Case report	3	Self-reported frequency of motor tics	50% to 70% remission	C	Sandyk et al57
Cannabis	Gilles de la Tourette Syndrome	Smoking	Case report	1	Self-reported symptoms	100% remission	C	Hemming et al58
Cannabis	Glaucoma	Smoking single dose	Double-blinded cross-over placebo-controlled RCT	18	Intraocular pressure	Significant reduction	B	Merritt et al59
Cannabis	Neuropathic pain in HIV patient	Smoking 5 days a week for 2 weeks	Prospective placebo-controlled RCT	28	Pain intensity using Descriptor Differential Scale	Improvement in pain (P = .016)	A	Ellis et al49
Cannabis	Sensory neuropathic pain in HIV patient	Smoking 3 times a day for 5 days	Double-blinded cross-over placebo-controlled RCT	50	Chronic pain ratings	Reduction of pain by 34% (P = .03)	A	Abrams et al48
Cannabis	Capsaicin-induced pain in volunteers	Smoking single dose at various concentrations	Double-blinded cross-over placebo-controlled RCT	15	Pain scores and McGill Pain Questionnaire	Pain reduction at medium dose within a certain time frame only	B	Wallace et al60
Cannabis	Acute inflammatory pain in volunteers	Single oral dose of encapsulate extract	Double-blinded cross-over placebo-controlled RCT	18	Threshold to heat and electricity in areas with UV-induced sunburnt	No effect on pain thresholds	B	Kraft et al61
Cannabis	Spasticity due to multiple sclerosis	Escalating dose of oral encapsulate extract	Double-blinded cross-over placebo-controlled RCT	50	Spasms frequency and mobility	Improvement in spasms frequency (P= .013) and mobility (P = .01)	A	Vaney et al62
Cannabis	Spasticity caused by multiple sclerosis	Titrating oral dose of cannabis extract	Double-blinded placebo-controlled RCT	327	Ashworth score and self-reported spasticity	Improvement of self-report ratings of pain and spasticity (P= .003)	A	Zajicek et al63
Δ9-THC	Gilles de la Tourette Syndrome	Single oral dose	Cross-over placebo-controlled RCT	12	TSSL, STSS, YGTSS scores	Significant reduction in TSSL score (P = .015), nil for STSS and YGTSS	A	Müller-Vahl et al64
Δ9-THC	Gilles de la Tourette Syndrome	Daily oral dose for 6 weeks	Placebo-controlled RCT	24	TSSL,TS-CGI, STSS; YGTSS	Significant reduction in TSSL score using ANOVA (P = .037), nil for TS-CGI, STSS, YGTSS	A	Müller-Vahl et al65
Δ9-THC	Spasticity caused by multiple sclerosis	Escalating dose for 5 days	Double-blinded cross-over placebo-controlled RCT	13	Subjective rating and objective measure of spasticity	Significant in both scores	A	Ungerleider et al66
Δ9-THC	Spasticity due to multiple sclerosis	Titrating oral dose of Δ9-THC	Double-blinded placebo-controlled RCT	330	Ashworth score and self-reported spasticity	Improvement of self-report ratings of pain and spasticity (P= .003)	A	Zajicek et al63
Δ9-THC	Postoperative pain	Single oral dose on postoperative day 2	Double-blinded placebo-controlled RCT	40	Summed pain intensity difference 6 hours after administration	No significant difference	B	Buggy et al67
Δ9-THC	Refractory neuropathic pain	Titrating oral dose	Open label pilot	8	Neuropathic pain score and quality of life	No apparent effect	C	Attal et al68
Δ9-THC	Glioblastoma multiforme	Daily intracranial tumour injection up to 64 days	Phase I cohort pilot study	9	Safety of intracranial route of administration	Intracranial route seems to be safe and may slow down tumour growth	C	Guzman et al69
Dronabinol (synthetic Δ9-THC)	Alzheimer's disease	Twice-daily oral dose for 6 weeks	Double-blinded cross-over placebo-controlled RCT	15	Body weight, triceps skin fold, disturbed behavior, affect	A trend of improvement reported but no significance quoted	B	Volicer et al70
Dronabinol (synthetic Δ9-THC)	Alzheimer's disease	Daily oral dose for 2 weeks	Open label pilot	6	Nocturnal motor activity score and Neuropsychiatric Inventory	Significant improvement in both (P = .028 and P = 0027)	C	Walther et al71
Dronabinol (synthetic Δ9-THC)	Anorexia and weight loss in AIDS	Twice-daily oral dose for 6 weeks	Placebo-controlled RCT	139	VAS for appetite, mood, and nausea	Significant change in appetite (38%; P = .015); mood (10%; P = .06); and nausea (20%; P = .05)	A	Beal et al72
Nabilone	Spasticity caused by spinal cord injury	Twice-daily oral dose for 4 weeks	Double-blinded cross-over placebo-controlled RCT	12	Ashworth Scale, Total Ashworth Score	Significant reduction, P= .003 and 0.001 respectively	A	Pooyania et al73
Nabilone	Pain caused by fibromyalgia	Oral dose for 4 weeks	Double-blinded placebo-controlled RCT	40	VAS and Fibromyalgia impact questionnaire	Significant reduction in both scores (P < .02)	A	Skrabek et al74
Sativex (extract of cannabis containing Δ9-THC and cannabidiol)	Peripheral neuropathic pain	Self-titrating dose of oromucosal spray for 5 weeks	Double-blinded placebo-controlled RCT	125	Various pain intensity scores	Significant reduction, (P= .001 to P= .04)	A	Nurmikko et al75
Sativex (extract of cannabis containing Δ9-THC and cannabidiol)	Intractable neurogenic symptoms	Self-titrating dose of oromucosal spray for 2 weeks	Double-blinded cross-over placebo-controlled RCT	20	Self-report symptoms and adverse effects	Significant relief in pain with certain domains reaching significance of P < .05	A	Wade et al76
Sativex (extract of cannabis containing Δ9-THC and cannabidiol)	Central pain in multiple sclerosis	Self-titrating dose of oromucosal spray for 4 weeks	Double-blinded placebo-controlled RCT	66	11-point scale for pain and sleep disturbance	Significant reduction of pain (P = .005) and sleep disturbance (P = .003)	A	Rog et al77
Sativex (extract of cannabis containing Δ9-THC and cannabidiol)	Bladder dysfunction in multiple sclerosis	Single daily dose for 8 weeks	Open label pilot study	15	Occurrence of urinary incontinence, frequency, nocturia	Significant reduction in all 3 domains (P< .05)	A	Brady et al78

RCT, randomized controlled trial; UV, ultraviolet; TSSL,; STSS,; YGTSS,; TS-CGI, ANOVA, analysis of variance; VAS, Visual Analog Scale; THC, tetrahydrolcannabinol.

The Challenges of using Cannabis

Despite the evidence of benefits in certain conditions, the use of medical marijuana within a legal jurisdiction still faces a number of challenges:

• Method of Delivery and Quality Control. Smoking raw cannabis remains the most common and easiest route of delivery, but the actual amount of cannabinoids deliverable to the alveolar space varies considerably depending on the individual's techniques of inhalation/exhalation, the percentage of aeroingestion, and the individual's functional lung capacity. Without prior training, it could be difficult for a family physician in daily practice to advise an eligible patient on the proper techniques of administration and quality control of prescription regarding medical marijuana. The content of THC in cannabis may vary remarkably according by geographic origin,^[56] the parts of plant being used (buds versus stem and seeds), the methods of storage, and the techniques of cultivation.^[79] There are 2 main strains used in medical marijuana: the Sativa and the Indica. The Sativa plant is usually taller with longer leaves that grow better outdoors, whereas the Indica plant is more bushy with shorter leaves that thrive better indoors. Although both strains exist in pure forms, various combinations of the 2 strains are packaged as medical marijuana, which may result in variable therapeutic and side effects. Health Canada's policy of adopting a centralized source of medical marijuana from an approved plantation is a good way to assure quality; however, it is still technically difficult to endorse it globally for all licensed users and growers. As a prescription, standardization and titration of dose efficacy remain a challenge for medical marijuana.
• Adequate Monitoring and Prevention of Addiction. As with other substances of abuse, cannabis may lead to varying adverse effects and addiction potential among different individuals. Before facilitating an eligible person to receive medical marijuana, family physicians should possess the knowledge and skills to screen for addiction potential. During the course of treatment, close surveillance of the patient to prevent addiction and adverse effects, in collaboration with a specialist when necessary, remains a top priority. In Canada and in those American states where it is legal to use medical marijuana, more training and educational resources should be made available for the practicing family physician to enhance their competence in approaching cannabis.
• Contaminants in Cannabis. Studies have reported an alarming level of biological contaminants in cannabis, which includeAspergillus fungus^[80,81] and bacteria,^[82] potentially leading to fulminant pneumonia, especially among the immunosuppressed.^[83] Nonbiological contaminants also have been found, which include heavy metals from soil like aluminum^[84] and cadmium, the latter of which seems to be absorbed by the cannabis plant in particularly high concentrations.^[85] Organophosphate pesticides are other nonbiological contaminants that are found less in cannabis cultivated outdoors than indoors.^[36] Finally, tiny glass beads or sand have been found in street samples of cannabis, which were added for weight to boost profits and can cause damage to the oral mucosa and lungs.^[86]
• Contamination by Cannabis. Secondary inhalation of cannabis fumes released by primary smokers is a theoretical but negligible threat, as shown by a study of airborne particulates in urban Spain^[87] and another study of passive exposure to cannabis smoke in a Netherlands coffee shop.^[88] More research in this area is warranted from the perspective of public health.

The Controversy Remains

In 1969, an article published in the New England Journal of Medicine quoted from the Wootton Report that cannabis is "a potent drug, having as wide a capacity as alcohol to alter mood, judgment, and functional ability, and admitted that it is a dangerous drug in that sense, but in terms of physical harmfulness much less dangerous than opiates, amphetamines, and barbiturates and also less dangerous than alcohol."^[89] Since then, scientific and clinical data have helped us understand the mechanisms of actions of cannabis and its derived compounds for treating chronic and neuropathic pain, highlighting the potential analgesic synergism with opioids and the potential of an opiate sparing effect in clinical settings. In particular, animal studies have recently shown that cannabidiol (CBD), a nonpsychoactive constituent of marijuana, is capable of decreasing self-administration and drug-seeking behavior caused by heroin,^[90] in addition to other anti-inflammatory antipsychotic and neuroprotective effects.^[91,92] Another observational study of the ratio of CBD:THC from street cannabis samples suggests that a higher CBD content reduced reinforcing behavior and attention bias to marijuana. Further directions of research include a better understanding of the mechanisms of action of CBD and its interplay with THC, plus bioengineering a safer marijuana strain that contains the appropriate composition of CBD and THC for optimal therapeutic effects with the least adverse profile and addictive potential. Thus, important issues of dosage standardization, quality control, adverse effects profiling, and prevention of addiction could be resolved. Until then, family physicians in North America and Canada continue to face the under-reported use of cannabis in our society and its risks of abuse.

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J Am Board Fam Med. 2011;24(4):452-462. © 2011 American Board of Family Medicine

A 52-year-old man with a history of hypertension presents for an elective subtotal colectomy for colon cancer. A recent workup identified a partially obstructing mass at the patient's splenic flexure. As an outpatient, he underwent a colonoscopy with a biopsy of the mass which revealed a moderately differentiated adenocarcinoma. At the time of admission, he denied any symptoms of constipation, diarrhea, abdominal pain, weight loss, or hematochezia. He has no history of heavy alcohol intake, tobacco use, or illicit drug use. He does not have a family history of malignancy. He undergoes a successful subtotal colectomy and ileocolic anastomosis, without any signs of complication. His immediate postoperative state is stable, but on postoperative day 5 he develops sudden-onset shortness of breath. He denies having any chest pain, palpitations, nausea, or diaphoresis.

On physical examination, his blood pressure is 132/74 mm Hg; his pulse is regular, with a rate of 105beats/min, and his respiratory rate is 30 breaths/min. His temperature is 98.7°F and his oxygen saturation is 90% on room air, which improves to 96% on 3 L of oxygen via nasal cannula. He is in mild respiratory distress but is able to speak in full sentences. He is not using the accessory muscles of respiration. The examination of his head and neck is normal. He has mildly decreased breath sounds at his right lung base. His heart examination demonstrates a normal S1 and S2 without murmurs or gallops. His abdomen is soft, nontender, and mildly distended with good bowel sounds; a midline incision scar is clean and nontender. He has palpable peripheral arterial pulses in his upper and lower extremities. The patient did not have edema or tenderness in the lower extremities.

The laboratory analyses, including a complete blood cell count and basic metabolic panel, are normal. An arterial blood gas on room air demonstrates a pH of 7.45, a pCO₂ of 32 mm Hg, and a pO₂ of 62 mm Hg, with an oxygen saturation of 93%. A chest x-ray reveals bibasilar subsegmental atelectasis. He is encouraged to perform incentive spirometry; however, his oxygen saturation deteriorates progressively and rapidly. On postoperative day 6 his hypoxemia is refractory to oxygen via a non-rebreather mask and he is intubated for hypoxemic respiratory distress and impending respiratory arrest. He is transferred to the ICU. His ECG shows an S1Q3T3 pattern and sinus tachycardia.

A 40-year-old man presents to the emergency department with a 5-day history of progressively worsening breathlessness on exertion and mild, general flulike symptoms. He also complains about night sweats and an intermittent low-grade fever, both of which started about 2 weeks ago.  This interesting case was actually misdiagnosed as early pneumonia caused by influenza.  The patient was treated with anti-influenza medication and was discharged home.  He returned two days later in a worsened condition.  Read more about this condition and how it was diagnosed.

An interesting case recently appeared in MedScape involving the sudden onset of a rapid heartrate in a woman.

A 61-year-old woman presents to the emergency department (ED) after being referred from her primary care provider's (PCP) office for evaluation of tachycardia. She had been seen by her PCP for routine placement of a purified protein derivative (PPD) tuberculin skin test and was incidentally noted to have a pulse of 160 beats/min. The patient currently denies any specific complaints other than occasional palpitations. On review of her systems, however, she notes having night sweats; a 110-lb (50-kg) weight loss over the preceding 12 months; and 2-3 months of anxiety, diarrhea, and occasional diplopia. She denies having any fever, chills, chest pain, dyspnea, or swelling in her extremities. She has a medical history of an unspecified thyroid problem. She does not take any daily medications and has no medication allergies. She has a 50-pack-year smoking history, with occasional alcohol consumption. She had been homeless for a time, but is currently living in an apartment.

On examination, the patient is awake and fully oriented. She is diaphoretic but in no apparent distress. Her temperature is 97.0°F (36.1°C); her pulse is 160 beats/min; her respiratory rate is 24 breaths/min, with an oxygen saturation of 98%; and her blood pressure is 190/117 mm Hg. She has bilateral exophthalmos with exotropia of the right eye. Her visual acuity and extraocular movements are intact. The neck examination reveals a diffuse, nontender goiter, without nodules or thyroid bruits. The heart is tachycardic, intermittently irregular, and without murmurs. The lungs are clear to auscultation bilaterally. The abdomen is nondistended, soft, and nontender, with no palpable masses. There is no edema of the extremities. The neurologic examination reveals normal mentation, intact cranial nerves, intact motor strength and sensation, and normal reflexes. No tremor is noted.

The initial laboratory studies reveal her complete blood cell count, electrolytes, renal function, and cardiac marker findings are all within normal limits. A plain chest x-ray is interpreted as normal (not pictured). An ECG is obtained which shows sinus tachycardia.

This patient's ECG showed atrial fibrillation with a rapid ventricular response, which is a possible cardiac manifestation of thyrotoxicosis. No ischemic changes were noted despite her rapid heart rate. Her laboratory studies confirmed the suspected diagnosis, with findings of a markedly depressed thyroid-stimulating hormone (TSH) level of 0.006 mIU/L (normal range, 0.5-5.0 mIU/L) and elevated triiodothyronine (T3) and thyroxine (T4) concentrations of 632 ng/dL (9.73 nmol/L) and 23.7 ug/dL (305.02 nmol/L), respectively (normal ranges, T3: 70-170 ng/dL; T4: 5-11 ug/dL).

Thyrotoxicosis refers to an elevated concentration of thyroid hormone as well as the related clinical manifestations. This is differentiated from thyroid storm, a life-threatening manifestation of thyrotoxicosis in which a markedly hypermetabolic state is present. Hyperthyroidism most commonly results from uncontrolled Graves disease, in which autoantibodies to the TSH receptor are produced. This leads to excessive thyroid hormone production from the thyroid gland and a reflexive inhibition of TSH release from the pituitary gland. Other etiologies can include a solitary thyroid adenoma, toxic multinodular goiter, hypersecretory thyroid carcinoma, thyrotropin-secreting pituitary adenoma, struma ovarii, and iodine or amiodarone administration. A precipitating event, such as surgery, trauma, myocardial infarction, pulmonary embolism, diabetic ketoacidosis, childbirth, severe infection, discontinuation of antithyroid medication, or thyroid surgery on a patient with uncontrolled hyperthyroidism, is often needed to push a patient with hyperthyroidism into thyroid storm.[1,2]

The incidence of hyperthyroidism in the United States is 0.05%-1.3%, most of which remains undiagnosed. Approximately 1%-2% of these patients will progress to thyroid storm at some point. The prevalence is slightly higher in women compared with men and in white and Hispanic populations compared with black populations. Thyroid storm is most common in the third to sixth decades of life, although it can occur at any age.[1]

Thyroid storm is a clinical diagnosis and, considering the acuity of this life-threatening condition, patients with thyrotoxicosis should be treated empirically when the diagnosis is suspected. Symptoms of thyrotoxicosis include weight loss, palpitations, hair loss, diplopia, chest pain, oligomenorrhea, or confusion. The physical examination reveals a hypermetabolic state, with abnormalities involving multiple organ systems. These findings commonly include hyperpyrexia, tachycardia, tachypnea, and hypertension. Other findings may include fine tremor, exophthalmos, ophthalmoplegia, pretibial edema, congestive heart failure, thyromegaly, thyroid bruit, and hyperreflexia.[3] Laboratory studies show a low TSH level and elevated T3 and T4 concentrations. TSH is the most precise indicator of thyroid function because of the very high sensitivity of the thyroid-pituitary feedback loop, and current assays are able to detect levels of 0.02 mIU/L or less. As such, a normal TSH level largely excludes significant thyroid disease. Other laboratory findings seen in thyrotoxicosis may include hyperglycemia, hypercalcemia, leukocytosis, and elevated liver enzymes.[2] Further testing may be indicated as part of a search for the precipitating cause of clinical decompensation, such as infection, myocardial infarction, or diabetic ketoacidosis. Electrocardiography most often reveals sinus tachycardia or atrial fibrillation. Although thyroid storm requires more rapid and aggressive therapy than thyrotoxicosis, differentiating between the 2 can sometimes be difficult, as it was in this patient. Burch and Wartofsky developed a scoring system to assist in making this distinction that takes into account thermoregulatory dysfunction, central nervous system effects, gastrointestinal dysfunction, the degree of tachycardia, the extent of congestive heart failure, the presence of atrial fibrillation, and the presence or absence of a precipitating event.[4]

Cardiac complications from thyrotoxicosis include arrhythmias, congestive heart failure, and pulmonary hypertension. The most common arrhythmia in thyrotoxicosis is sinus tachycardia; however, atrial fibrillation occurs in 10%-20% of patients with thyrotoxicosis, most often in patients who are older than 60 years of age. Risk factors for atrial fibrillation in these patients include male sex, increasing age, coronary heart disease, heart failure, and structural heart or valvular disease. Congestive heart failure in thyrotoxicosis is predominantly caused by either persistent tachyarrhythmias (tachycardia-induced cardiomyopathy) or uncontrolled hypertension as a consequence of thyrotoxicosis. Systolic dysfunction can occur as a consequence of the persistent cardiac arrhythmias, but it usually resolves once the hyperthyroid state is treated. Pulmonary hypertension can also occur in thyrotoxicosis, either as a result of a primary effect of thyroid hormone on pulmonary arteriolar resistance vessels, decompensated left heart failure, or via increased pulmonary arterial blood flow (high-output).[1]

The differential diagnosis for thyrotoxicosis and thyroid storm may include anxiety, congestive heart failure, heat exhaustion or heatstroke, factitious disorder, neuroleptic malignant syndrome, panic disorder, septic shock, serotonin syndrome, anticholinergic or sympathomimetic toxicity, and alcohol or benzodiazepine withdrawal syndromes.[5] Because infection is a common trigger for thyroid storm, an initial misdiagnosis of sepsis is not uncommon because of similar characteristics, such as tachycardia, fever, and altered mental status.

Management of thyrotoxicosis consists of a 5-pronged, ordered approach, targeting each step in the biosynthetic pathway of thyroid hormone and its activity on target tissues. Treatment begins with administration of propylthiouracil (PTU) or methimazole, both of which act by inhibiting new hormone synthesis. PTU has the added effect of decreasing peripheral T4 to T3 conversion. Beta-blockers are then used to inhibit target activity of thyroid hormone. Propranolol is the preferred agent because it also blocks peripheral conversion of T4. When cardioselective agents are preferred, atenolol or metoprolol may be used. At least 1 hour after administration of PTU or methimazole, the patient may be given iodide to inhibit further thyroid hormone release. It is imperative that iodine be given only after synthesis of new hormone is blocked because iodide administration can have the undesired effect of increasing new hormone synthesis. Potassium iodide or Lugol solution of iodine is recommended. Peripheral conversion of T4 to T3 is blocked, as noted above, and dexamethasone may be used as well. Further treatment is supportive and may include acetaminophen for fever and hydrocortisone if the patient is hypotensive as a result of adrenal insufficiency. Salicylates are contraindicated because they displace bound thyroid hormone in the blood.[2,3]

With regard to the management of cardiac symptoms related to thyrotoxicosis, treatment is focused on reducing adrenergic drive to the heart and restoring normal cardiac rhythm. As mentioned above, beta blockers are very effective for rapid hemodynamic improvement. Either propranolol or metoprolol given intravenously can be used to improve heart rate control either in sinus tachycardia or atrial fibrillation. In severe cases, a continuous infusion of esmolol may be required for rate control. Amiodarone should be avoided when treating atrial fibrillation from thyrotoxicosis because of its high iodine content, which may induce or exacerbate thyroid storm.

If a patient is hemodynamically unstable from atrial fibrillation, direct current cardioversion should be used. If symptoms of pulmonary congestion appear, diuretics may be used. Other drugs for heart failure (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and/or aldosterone receptor antagonists) are reasonable agents in patients who have depressed left ventricular systolic function. Anticoagulation is recommended for patients in atrial fibrillation secondary to thyrotoxicosis. The 2006 American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines recommend anticoagulation with warfarin to an international normalized ratio of 2.0-3.0 until the patient is euthyroid, after which recommendations and risk stratification are the same as those for atrial fibrillation without thyrotoxicosis.[3] Of note, PTU, methimazole, and iodide solutions are all classified as pregnancy class D and, as such, should not be used in pregnancy.

This patient's clinical presentation bordered between thyrotoxicosis and thyroid storm, and she was hemodynamically stable. She was immediately treated with propranolol and PTU and was admitted to a monitored bed in the medical service. Because her clinical condition improved and she remained stable, the admitting team chose to forgo further therapy with iodine and steroids. Her atrial fibrillation resolved within 12 hours, but an echocardiogram revealed cardiomyopathy with a left ventricular ejection fraction of 45% that was attributed to her long-standing hyperthyroidism. A diagnosis of Graves disease was made. She was continued on methimazole and metoprolol, and anticoagulation was initiated. Five months later, the patient was still taking methimazole. Her thyroid function had normalized, her cardiomyopathy had reversed, and her anticoagulation was discontinued, because atrial fibrillation did not recur. Incidentally, she was ruled out for tuberculosis during her admission with 3 induced sputum samples.

References

1. Schraga ED. Hyperthyroidism, thyroid storm, and Graves disease. eMedicine from WebMD: Emergency Medicine. Last updated April 23, 2010. Available at: http://emedicine.medscape.com/article/767130-overview Accessed January 28, 2011.
3. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35:663-686. Abstract
5. Fuster V, Rydén LE, Cannom DS, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257-354. Abstract
7. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22:263-277. Abstract
9. Pimentel L, Hansen KN. Thyroid disease in the emergency department: a clinical and laboratory review. J Emerg Med. 2005;28:201-209. Abstract

Background

A 61-year-old white man presents to the emergency department with a 1-week history of diffuse "crampy" abdominal pain. For the past 2 months, he has had diarrhea and has been passing blood with every bowel movement, either on the stool surface or separately from the stool. Recently, he has had 10-15 loose stools per day, with associated urgency and tenesmus. He has lost 4 lb in the past week. He feels lightheaded upon standing and is experiencing fatigue and mild shortness of breath. He takes atorvastatin for hypercholesteremia and acetaminophen for intermittent back and knee pain. He is allergic to penicillin. He has no history of gastrointestinal tract disease; screening colonoscopy performed 2 years ago was unremarkable. His father died of myocardial infarction when he was in his 60s, and his mother died of breast cancer when she was in her 40s. He has no siblings. He is retired from his work as an accountant and lives with his wife. He has not travelled recently. He has a 25-pack-year smoking history but has not smoked for approximately 10 years. He drinks alcohol on social occasions and on weekends, and he denies illicit drug abuse.

On physical examination, the patient is a pale, diaphoretic man in some distress due to abdominal pain. His oral temperature is 101.5°F (38.6°C), blood pressure is 110/62 mm Hg, pulse is 107 beats/min, and respiratory rate is 24 breaths/min. His body mass index is 29.7 kg/m². Examination of his head and neck is unremarkable aside from pale mucosal membranes. Lung auscultation reveals normal breath sounds, with no crackles or rhonchi. His heart rate is tachycardic, and his heart rhythm is regular. There are no murmurs or extra heart sounds. His abdomen is distended and firm, with diffuse rebound tenderness that seems worse in the lower left quadrant. Bowel sounds are diminished. No hepatosplenomegaly, ascites, or palpable masses are appreciated. Digital rectal examination demonstrates normal rectal tone, "velvety" rectal mucosa, and bright red blood on withdrawal of the examining finger. There is pitting edema of the legs and feet.

Laboratory analysis includes a complete blood count (CBC), which demonstrates anemia (hemoglobin concentration of 6.7 g/dL [67 g/L]), leukocytosis (leukocyte count of 14.2 x 10³ cells/μL [14.2 x 10⁹ cells/L]), and thrombocytosis (platelet count of 540 x 10³ cells/µL [540 x 10⁹ cells/L]). Additional findings include elevations in the erythrocyte sedimentation rate (78 mm/h) and C-reactive protein level (114 mg/L). His albumin level is low, at 2.0 g/dL (20 g/L). The basic metabolic panel is unremarkable. Repeat stool cultures and samples for ova and parasites are negative. Flexible sigmoidoscopy shows diffusely erythematous and friable colonic mucosa with large ulcerated patches, abundant yellow-white exudate, and oozing blood. These findings extend in a proximal and continuous fashion from the rectum to at least the middle of the sigmoid colon. Tissue biopsy samples sent for histopathologic examination reveal lymphoplasmacytic inflammation along the base of the crypts; neutrophils that infiltrate the crypt epithelium and collect in the depths of the colonic crypts to form "crypt abscesses"; and focal chronic reactive changes, including crypt branching, gland atrophy, and goblet-cell mucin depletion. No granulomas are identified.

Discussion

The diagnosis of fulminant inflammatory bowel disease was initially suspected on the basis of the patient's history, physical examination, and laboratory test results; endoscopic and biopsy findings confirmed the diagnosis. The rectal bleeding was bright red, indicating that the source of the bleeding was most likely the lower gastrointestinal tract. The concurrent presence of crampy abdominal pain, diarrhea, tenesmus, and fever suggested that an inflammatory process had damaged the colonic mucosa. The unremarkable colonoscopy findings 2 years before presentation rendered a neoplasm unlikely. Although not impossible, it is rare for colon cancer to present with diarrhea. Most compelling was the continuity and character of the mucosal damage identified on endoscopy and the histopathologic findings, which were diagnostic of ulcerative colitis. Symptom duration suggested a chronic inflammatory process and infectious causes of colitis had been ruled out.

Ulcerative colitis is estimated to respectively have an incidence of 7.3 and prevalence of 116 per 100,000 people in the United States.[1] The peak age at onset is 15-25 years, with a second peak at 40-60 years.[2] Individuals of Ashkenazi Jewish or Scandinavian descent are more often affected, with men and women experiencing a similar disease incidence. Smoking seems to play a protective role against the development of ulcerative colitis, and it has been proposed that the second incidence peak in part represents patients who stopped smoking at a later age.[3] Most research suggests that the etiology and pathogenesis of ulcerative colitis are multifactorial, with a combination of genetic susceptibility, bacterial antigens, and alteration of mucosal immunity responsible for the development of the disease.[4]

The diagnosis of fulminant inflammatory bowel disease was initially suspected on the basis of the patient's history, physical examination, and laboratory test results; endoscopic and biopsy findings confirmed the diagnosis. The rectal bleeding was bright red, indicating that the source of the bleeding was most likely the lower gastrointestinal tract. The concurrent presence of crampy abdominal pain, diarrhea, tenesmus, and fever suggested that an inflammatory process had damaged the colonic mucosa. The unremarkable colonoscopy findings 2 years before presentation rendered a neoplasm unlikely. Although not impossible, it is rare for colon cancer to present with diarrhea. Most compelling was the continuity and character of the mucosal damage identified on endoscopy and the histopathologic findings, which were diagnostic of ulcerative colitis. Symptom duration suggested a chronic inflammatory process and infectious causes of colitis had been ruled out.

Ulcerative colitis is estimated to respectively have an incidence of 7.3 and prevalence of 116 per 100,000 people in the United States.[1] The peak age at onset is 15-25 years, with a second peak at 40-60 years.[2] Individuals of Ashkenazi Jewish or Scandinavian descent are more often affected, with men and women experiencing a similar disease incidence. Smoking seems to play a protective role against the development of ulcerative colitis, and it has been proposed that the second incidence peak in part represents patients who stopped smoking at a later age.[3] Most research suggests that the etiology and pathogenesis of ulcerative colitis are multifactorial, with a combination of genetic susceptibility, bacterial antigens, and alteration of mucosal immunity responsible for the development of the disease.[4]

Histopathologically, ulcerative colitis is characterized by lymphoplasmacytic inflammation of the mucosa and submucosa, with scattered neutrophils in the lamina propria (Figure 1). The neutrophils typically injure the crypt epithelium and may collect in the base of the crypts, forming crypt abscesses (Figure 2). Within weeks of disease onset, features of crypt architectural distortion (such as crypt branching and shortening) develop; these chronic changes are a nonspecific regenerative response to previous injury. Deep granulomas and transmural inflammation, 2 hallmarks of Crohn's disease, do not occur.[5]

Classically, ulcerative colitis is insidious in onset. Affected patients present with frequent passage of bloody, loose stools and tenesmus. The intensity of the symptoms generally correlates with the extent of anatomic involvement, allowing classification of disease as mild, moderate, or severe/fulminant. The majority of patients have mild, indolent disease limited to the rectum and sigmoid colon that is characterized by diarrhea, intermittent rectal bleeding, and tenesmus. The physical examination is often normal aside from bright red blood within the rectum. Other patients present with systemic symptoms, including more frequent bowel movements, crampy abdominal pain, decreased bowel sounds, high-grade fever, tachycardia, anemia, orthostatic hypotension, and weight loss. Extraintestinal manifestations, such as acute arthropathy, episcleritis, erythema nodosum, and pyoderma gangrenosum may also arise. Fewer than 10% of patients with ulcerative colitis initially present with fulminant disease, with older individuals represented in greater numbers. Fulminant ulcerative colitis is more abrupt in onset and is usually characterized by extensive colonic involvement ("pancolitis"), with rectal bleeding that may be extensive enough to necessitate blood transfusion. Abdominal distention and tenderness to palpation with signs of peritoneal inflammation (eg, rebound tenderness) may be observed in these patients. Of greatest concern in patients with fulminant disease is the prospect of massive hemorrhage, toxic megacolon, or bowel perforation. Immediate hospitalization is often necessary in these patients.

The differential diagnosis of bright red blood in the rectum associated with diarrhea includes infectious colitis, ischemic colitis, and nonsteroidal anti-inflammatory drug enteropathy. Other causes of colonic bleeding, such as diverticular disease, can present with loose stools, because blood is a cathartic. Stool studies (eg, fecal leukocytes, culture, ova, and parasites) and a Clostridium difficile toxin screen should be considered to eliminate the possibility of infectious colitis. A complete blood cell count should be obtained to evaluate for anemia or leukocytosis. Low albumin levels signify poor nutritional status and protein-losing enteropathy. A basic metabolic panel may demonstrate electrolyte abnormalities in the setting of severe prolonged diarrhea. Inflammatory markers, such as the erythrocyte sedimentation rate and C-reactive protein level, are typically elevated in patients with inflammatory bowel disease. Radiographic studies may be used as an adjunct in diagnosing complications of ulcerative colitis (eg, plain films can establish the presence of toxic megacolon). In the setting of acute flares, other radiologic studies, such as computed tomography (CT), may be done to evaluate for an alternative diagnosis. Common CT findings in ulcerative colitis include thickening of the colonic wall, pericolonic fat stranding, and a "target" appearance of the rectum. Most important in confirming the diagnosis of ulcerative colitis is flexible sigmoidoscopy with biopsy; colonoscopy may also be used in some settings, but it is associated with a higher risk for perforation and is contraindicated in cases of suspected toxic megacolon. Typical endoscopic findings in ulcerative colitis patients include diffuse erythema; edema; friability; and granularity of the mucosa, with loss of the normal vascular pattern. Ulceration with exudate and pseudopolyps are frequently identified as well. These findings invariably begin in the rectum and extend proximally in a continuous manner, up to and including the cecum, in cases of pancolitis.[6]

In most cases, ulcerative colitis can be managed in the outpatient setting. Treatment is designed to achieve and maintain disease remission. Topical therapy and 5-aminosalicylic acid (ASA) agents are the first-line means of treating ulcerative colitis, with steroids for acute flares and immunomodulators as maintenance therapy in severe refractory disease. Fulminant ulcerative colitis requires careful attention to the development of toxic megacolon. Parenteral corticosteroids; rehydration; bowel rest; nutritional supplementation; anticoagulation with low-dose heparin to prevent venous thrombosis, which is common in patients with ulcerative colitis; and monitoring of hemoglobin values (with transfusion sometimes required) are recommended. If remission is achieved, a maintenance regimen consisting of immunomodulators (such as cyclosporine, 6-mercaptopurine, or azathioprine) and/or 5-ASA should be initiated. In patients with fulminant ulcerative colitis that is refractory to first-line therapy, infusion of a biologic agent (such as infliximab) or colectomy may be necessary.[7]

The patient in this case was immediately admitted to the hospital because of concerns that he was at risk for massive hemorrhage, toxic megacolon, or bowel perforation. Three units of cross-matched blood were transfused, and he was prescribed bowel rest, peripheral hyperalimentation, and prednisolone. Shortly thereafter, 5-ASA was added to his therapeutic regimen. His symptoms resolved gradually, and he was discharged to home. Over the next few years, he experienced several disease flares, and the benefits and risks of immunomodulators and biologic agents versus colectomy were reviewed with him during a particularly severe flare. After considerable reflection, he decided in favor of colectomy; the patient tolerated the operation well. Gross examination of the colectomy specimen demonstrated involvement of the entire colon from cecum to anus. Multiple irregular ulcers with an associated yellow-white exudate were scattered throughout the colon, and diffuse pseudopolyps (Figure 3) were present. Findings consistent with Crohn's disease (eg, fissures, fistulas, perianal involvement, "creeping fat," and segmental disease) were not identified. As expected, the procedure resulted in complete remission of the patient's symptoms. After ileal pouch anal anastomosis surgery, most patients can expect to have 4-6 loose bowel movements per day.

References

1. Farrokhyar R, Swarbrick ET, Irvine EJ. A critical review of epidemiological studies in inflammatory bowel disease. Scand J Gastroenterol. 2001;36:2-15. Abstract
2. Ekbom A, Helmick C, Zack M, Adami HO. The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. Gastroenterology. 1991;100:350-358. Abstract
3. Tuvlin JA, Raza SS, Bracamonte S, et al. Smoking and inflammatory bowel disease: trends in familial and sporadic cohorts. Inflamm Bowel Dis. 2007;13:573-579. Abstract
4. Lukas M, Bortlik M, Maratka Z. What is the origin of ulcerative colitis? Still more questions than answers. Postgrad Med J. 2006;82:620-625. Abstract
5. Odze RD, Goldblum JR. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009.
6. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 8th ed. Philadelphia, PA: Saunders Elsevier; 2006.
7. Sands BE. Fulminant colitis. J Gastrointest Surg. 2008;12:2157-2159. Abstract

Whiplash injuries are a frequent cause of chronic neck and back pain and are common cases in the personal injury litigation arena.  Litigation of these cases is often predicated on science as much as it is predicated on the facts of the case.  The study below was recently published in Spine Journal, and will give some clarity about those factors that affect the development of chronic neck pain status post a rear-end motor vehicle accident.

Eulogio Pleguezuelos Cobo, MD; M. Engracia Pérez Mesquida; Elisabet Palomera Fanegas; Eva Moreno Atanasio; M. Beatriz Samitier Pastor; Cristina Perucho Pont; Carlos Matarrubia Prieto; Genoveva Reverón Gómez; Lluis Guirao Cano

Spine. 2010;35(9):E338-E343

Abstract and Introduction

Abstract

Study Design. Prospective longitudinal study.
Objective. To identify prognosis factors that allow us to identify patients with risk of developing chronic symptoms and disabilities after a whiplash injury.
Summary of Background Data. The prognosis factors for poor recovery in acute whiplash are not conclusive.
Methods. We included 557 patients who suffered whiplash injury after road traffic accident and visited the Department of Physical Medicine and Rehabilitation of Mataró Hospital (Spain) for medical evaluation and rehabilitation treatment. The variables were collected following a protocol designed for the study, and all patients were assessed through the Visual Analogue Scale (VAS) for the intensity of neck pain, the Goldberg Depression and Anxiety Scale and the Northwick Park Neck Pain Questionnaire (NPH) for cervical column functionality at initial evaluation and 6 months later.
Results. Factors related with VAS 6 months after the whiplash injury were women, age, number of days of cervical column immobilization, previous neck pain, self-employed workers, housewives, pensioners, students, presence of headache or dizziness, and VAS, Goldberg Depression and Anxiety scale, and NPH scores at initial evaluation. In multivaried analysis, it had been found that the variables that had influence on VAS 6 months after the whiplash injury were statistically significant for age, presence of dizziness, self-employed workers, and VAS and NPH scores at initial evaluation.
Conclusion. Our findings indicate that factors that allow us to identify patients at risk for poor recovery are age, dizziness, and initial evaluation of neck pain with VAS and cervical column functionality with NPH.

Introduction

The whiplash is a cervical column injury, which is caused when the neck is violently extended, generally produced in vehicle collisions. It was described first time by Crowe in 1928.^[1] After the Quebec Task Force on whiplash-associated disorders (WAD) study, whiplash was defined as a set of symptoms that appear after an acceleration-deceleration mechanism of energy transfer to the neck. That energy transfer mechanism may be caused by road collisions between vehicles, but it could also occur in other circumstances (i.e., diving). The energy transferred results into bone or soft tissue injuries, which could invariably lead to a variety of clinical symptoms.^[1]

The incidence is variable in different geographical areas.^[1] In the United States, 3 cases per 1000 inhabitants are diagnosed of this disease per year,^[2] in Norway, 2 cases per 1000 inhabitants per year,^[3] in Australia, 1 case per 1000 inhabitants per year,^[4] and in Quebec, 0.7 cases per 1000 inhabitants per year.^[4]

The main characteristic of this syndrome is the absence of evidence of pathology findings as detected in different imaging techniques despite the traumatism intensity, symptoms, and clinical findings. This poor evidence carries along with important social and sanitary problems. Although we could say that whiplash is a benign pathology, we should also consider that this is a disease with an high impact on health public, because the huge number of incapacities produced are defrayed by the public coffers with an estimated expenditure to the tune of 10,000 million euros per year in Europe, whereas in the United States, the numbers could rise between 4.5 and 29 billion dollars.^[5,6]

On the other hand, prognostic factors in whiplash injury can be either magnified or hidden because of the existence of court cases to obtain economic compensations. Cassidy et al^[7] showed that there is a diminution in the incidence of whiplash, being up to 28% in those patients with a better prognostic, when compensation laws regarding accidents were modified. In the literature, there are no unified criteria to identify those patients with risk of developing chronic symptoms and disabilities in the whiplash injury. The goal of this prospective longitudinal study is to identify prognostic factors for poor recovery in whiplash injury after initial evaluation at Department of Physical Medicine and Rehabilitation (DPMR), considering pain as the main variable of the study.

What are the medical legal implications of the following case?

A 43 year-old man presents to the emergency department (ED) complaining of a severe frontal headache that began suddenly and awakened him from sleep. The headache is associated with nausea, vomiting, and fevers. He also complains of new-onset diplopia (double vision) and photophobia (bright light bothers him), but denies any decrease in visual acuity. He denies experiencing any associated seizures, focal weaknesses, previous similar episodes, frequent headaches, or previous visual disturbances. He does not have any prior significant medical problems, and takes no medication. He drinks socially, does not smoke, and denies recreational drug use.

On physical examination, the patient is ill-appearing but alert and in no apparent distress. His vital signs reveal a temperature of 103.1°F (39.5°C), a blood pressure of 155/95 mm Hg, and a pulse of 110 bpm. The ocular examination demonstrates ptosis of the right eye (droopy eyelid), which is deviated inferolaterally and has a dilated and unreactive pupil. The visual field examination demonstrates bitemporal hemianopsia. Funduscopic examination shows normal venous pulsation and mild bilateral temporal disc pallor. The cranial nerves are otherwise without deficit. The neck is supple and without meningismus. Examination of the chest reveals mild bilateral gynecomastia, without nipple discharge. The lungs are clear to auscultation. Cardiac auscultation reveals a normal S1 and S2 and no murmurs, rubs, or gallops. The abdomen is soft and nontender, and no organomegaly is detected. Bilateral upper and lower extremity strength is 5/5, with normal deep tendon and plantar reflexes. The patient's sensation is intact to light touch and pinprick throughout, and the gait is normal.

Laboratory investigations reveal a hemoglobin concentration of 13 g/dL (130 g/L); a white blood cell (WBC) count of 16.0 × 10³/µL (16.0 × 10⁹/L), with 75% neutrophils; and a platelet count of 340 × 10³/µL (340 × 10⁹/L). The electrolyte, blood urea nitrogen (BUN), creatinine, and glucose examinations are all within normal limits. Cerebrospinal fluid (CSF) specimens show 420,000 red blood ceels (RBC)/μL, 20,000 WBC/μL, a normal glucose of 85 mg/dL (4.72 mmol/L), and an elevated protein concentration of 230 mg/dL (2.3 g/L). The CSF Gram stain is negative for bacteria. A computed tomography (CT) scan of the brain is performed, followed immediately by magnetic resonance imaging.

The radiologist misreads the films and the patient is given fever reducing medication and sent home by the emergency physician.  He is told to visit his family physician in a few days.  The following day, he is found unconscious and is returned to the hospital by ambulance.  He is admitted in critical condition and he is re-evaluated.  Re-evaluation included a re-examination of his imaging studies by other radiologists.

He is admitted to the ICU undergoes a surgical procedure, but he never regains consciousness, although his vital signs are stabilized.  He remained in a vegetative state.  The family sued the physicians and the hospital for malpractice.

Discussion

The noncontrast CT scan of the brain when re-reviewed showed a 2-cm sellar mass, with suprasellar extension. There was impingement on the optic chiasm and the hypothalamus, with upward displacement. There was increased density on the right side of the mass, which was suggestive of hemorrhage. The sagittal and coronal T1- and T2-weighted MRI scans demonstrated a large soft-tissue mass in the pituitary fossa, with areas of intermediate- and high-intensity signal suggestive of hemorrhage (see Figure 3). Coronal gadolinium-enhanced T1-weighted images revealed that the mass had a heterogeneous pattern of faint peripheral enhancement (Figure 4). There was evidence of mass effect on the right cavernous sinus, which was most evident in the coronal T1- and T2-weighted images. These findings are consistent with pituitary apoplexy as a result of hemorrhage with or without infarction, likely into a pituitary adenoma. Tests for evaluating the hormonal status of the patient revealed panhypopituitarism. Prior to the acute apoplectic episode, the patient had findings suggestive of central hypogonadism, probably as a component of his hypopituitarism caused by pituitary macroadenoma (diminished libido and bilateral gynecomastia). His neurologic finding (right-sided ptosis with a fixed and dilated pupil pointing downward and outward) was consistent with a right-sided 3rd nerve palsy caused by extension of hemorrhage into the right cavernous sinus.

Pituitary tumor apoplexy is defined as hemorrhage or infarction of a pituitary gland associated with the presence of a preexisting pituitary adenoma. It manifests as a sudden, severe headache, and it is sometimes associated with neurologic and hormonal dysfunction. The word "apoplexy" stems from a Greek term meaning to "have a stroke".[1] Neurologic symptoms and signs are secondary to displacement of the optic nerve and impingement of the 3rd, 4th, and 6th cranial nerves. Hormonal dysfunction results from destruction of the anterior pituitary gland.

Pituitary tumor apoplexy is a rare disorder with an annual incidence of about 1.2 per million.[2] Men are affected twice as often as women, and all age groups can be affected, with the majority of patients in the 5th or 6th decades of life.[3] It is estimated to occur in 1.5-27.7% of cases of pituitary adenoma.[4] Pituitary tumor apoplexy is only rarely associated with a healthy gland; however, approximately 50% of patients who present with pituitary tumor apoplexy are not diagnosed with a pituitary lesion prior to their presentation.[1] All types of pituitary tumors carry the same risk for apoplexy.

The most common symptom of pituitary tumor apoplexy is headache. Almost all patients describe a sudden, severe retro-orbital or bifrontal headache, which is associated with vomiting in two-thirds of cases.[4] The headache and vomiting result from the sudden increase in intrasellar pressure either caused by the hemorrhage or secondary to meningeal irritation from blood or tumor products that leak into the CSF. The increase in intrasellar pressure results in many of the symptoms and signs of pituitary tumor apoplexy.[5] Laterally, the increased pressure causes compression of the structures in the cavernous sinus, namely the 3rd, 4th, and 6th cranial nerves, with the 3rd being most commonly affected as a result of its vulnerable position (parallel to the lateral wall of the pituitary gland). The 6th cranial nerve is the least commonly involved because of its most lateral location within the sinus.

Ophthalmoplegia (caused by 3rd, 4th, and 6th nerve palsies or any combination thereof) is present in around 80% of patients presenting with pituitary tumor apoplexy.[4] Also located within the cavernous sinus is the trigeminal nerve; its involvement may cause facial pain or sensory loss. Carotid siphon compression may present as hemiplegia. Superiorly, the increased pressure compresses the optic chiasm, optic tract, or optic nerve, leading to decreased visual acuity or visual field defects (classically, bitemporal hemianopsia). Blood leaking into the subarachnoid space may result in chemical meningitis with fever, meningismus, and photophobia. Fever in patients with apoplexy may also be explained by alteration in thermal regulation caused by hypothalamic involvement by the hemorrhage or by adrenal insufficiency associated with hypopituitarism. Hemorrhage may extend into the brain parenchyma causing cortical irritation and provoking seizures.

The elevated intrasellar pressure also accounts for the endocrine abnormalities found in cases of pituitary tumor apoplexy. This pressure increase results in compression of the pituitary tissue, compromising its vascular supply and leading to hypopituitarism. Adrenal insufficiency is the most clinically significant result of hypopituitarism, contributing significantly to the mortality of patients with pituitary tumor apoplexy if not promptly recognized and treated. Although not common, patients with pituitary tumor apoplexy may have diabetes insipidus at presentation. The true etiology of diabetes insipidus in this setting is unknown, but it may result from the increased pressure on the pituitary infundibulum, which impedes the antidiuretic hormone from passing from the hypothalamus to the posterior lobe of the pituitary.

A precipitating factor is identified in 50% of cases of pituitary tumor apoplexy. Predisposing factors include dopamine agonist treatment, head trauma, pituitary irradiation, pregnancy, coronary artery bypass grafting, surgical operations, and anticoagulation. Endocrine stimulation tests are also associated with pituitary tumor apoplexy. It is postulated that hormones used in these tests may increase blood flow in pituitary adenomas, provoking bleeding in friable vessels. Pituitary tumor apoplexy following childbirth associated with significant postpartum hemorrhage in nontumorous glands is termed "Sheehan syndrome". The hypertrophy of the pituitary gland that occurs in normal pregnancy combined with the arterial spasm of the pituitary's blood supply (caused by bleeding and hypotension) both contribute to the development of Sheehan syndrome; however the clinical presentation of pituitary apoplexy in these cases is usually less dramatic, with a more gradual development of signs and symptoms of hypopituitarism.

The diagnosis of pituitary tumor apoplexy is best established by MRI; however, this is usually preceded by a rapid diagnostic CT scan to screen for intracranial hemorrhage. MRI is superior to CT scanning for evaluating the pituitary gland and possibly visualizing hemorrhage not seen by CT. In one study, the detection rate of pituitary tumor apoplexy by CT scanning was 21%, whereas the detection rate was 100% with MRI.[3]

Once recognized, effective treatment of pituitary tumor apoplexy requires prompt administration of high-dose corticosteroids. Steroids should be administered in supraphysiologic doses to not only replace endogenous hormone deficiency during a stressful condition, but also to take advantage of its anti-inflammatory effect by decreasing swelling on parasellar structures. The definitive treatment for pituitary tumor apoplexy is emergent surgical decompression. Transsphenoidal resection is the most common approach in this situation. In cases where there is significant extension of hemorrhage into the brain parenchyma beyond the diaphragma sella, an intracranial approach may be preferred. In a minority of cases, conservative medical therapy is an acceptable alternative; examples of this include patients who are poor surgical candidates and selected patients who present with isolated meningismus or ophthalmoplegia and show significant improvement with steroid administration. Medical management includes monitoring of endocrine, neurologic, and ophthalmologic function combined with hormone replacement.

With prompt recognition, timely surgery, and proper medical management, the majority of patients with pituitary tumor apoplexy improve.[6] Ophthalmoplegia is usually the first symptom to resolve. Less readily restored is the optic nerve defect resulting in decreased visual acuity and restricted visual fields. More than half of patients, however, will have permanent hormone deficiencies resulting from pituitary injury and will require hormone replacement. One study showed that maintenance steroid, thyroid hormone, and testosterone replacement was essential postoperatively in 82%, 89%, and 64% of patients, respectively.[7]

Following immediate administration of high dose corticosteroids, the patient in this case underwent an emergent transsphenoidal resection. An infarcted adenoma was identified, with extensive areas of hemorrhage and necrosis consistent with apoplexy. After surgery the swelling in the brain worsened and he remained in a coma. An endocrinology evaluation was completed, and the patient was confirmed to have hypopituitarism, but suffered the effects of significant intracranial bleeding.

The plaintiff's theory of the case was that a correct diagnosis would have resulted in immediate surgery before the patient had bled to a degree where he has lost brain function and consciousness.  The jury agreed.  The case was taken to court where a plaintiff verdict was returned.

References

1. Verrees M, Arafah B, Selman WR. Pituitary tumor apoplexy: characteristics, treatment, and outcomes. Neurosurg Focus. 2004;16:E6.
2. Nielsen EH, Lindholm J, Bjerre P, et al. Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma. Clin Endocrinol (Oxf). 2006;64:319-22.
3. Randeva HS, Schoebel J, Byrne J, Esiri M, Adams CB, Wass JA. Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf). 1999;51:181-8.
4. Vaphiades MS. Pituitary Apoplexy. eMedicine from WebMD. Last Updated: August 6, 2009. Available at: http://emedicine.medscape.com/article/1198279-overview.
5. Zayour DH, Selman WR, Arafah BM. Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function. J Clin Endocrinol Metab. 2004;89:5649-54.
6. Dubuisson AS, Beckers A, Stevenaert A. Classical pituitary tumour apoplexy: clinical features, management and outcomes in a series of 24 patients. Clin Neurol Neurosurg. 2007;109:63-70.
7. Veldhuis JD, Hammond JM. Endocrine function after spontaneous infarction of the human pituitary: report, review, and reappraisal. Endocr Rev. 1980;1:100-7.

Toxicologists are often faced with cases where the subject in question had altered mental status as a consequence of the effects of illicit substances.  In this setting, dealing with aggressive patients can make a big difference in outcome. Patient death or injury resulting from the use of restraint and seclusion is an increasing concern in the field and in prison. Excessive and inappropriate TASER use has also been associated with sudden death.  A well-known 1998 article[1] documented 142 restraint-related deaths nationwide over a decade, 40% of which were attributed to unintentional asphyxiation during restraint. Restraint not only poses a risk for patient harm but also is physically and emotionally traumatizing for staff involved in the incident. Stefan pointed out that "high restraint rates are now understood as evidence of treatment failure."[2] Since the Joint Commission began tracking sentinel events in 1996, it has reviewed the deaths of 20 patients who were physically restrained.[3] Since then, the Joint Commission has advocated standards based on prevention as an intervention and the use of restraint as a last resort only after the least restrictive measures are exhausted.

Most communities have a protocol to call for team assistance when a psychiatric patient begins to display aggression or when an ordinarily calm individual becomes agitated while on excitatory drugs such as methamphetamine, cocaine, or phencyclidine. Law enforcement often believe that there is power in numbers, which can be true in certain situations. However, the increased external stimuli of gathering more police officers can also have untoward effects on the patient. The show of force may contribute to the escalation of combative behaviors.

Evidence points to a direct correlation between a high level of anxiety or perceived powerlessness on the patient's part and ensuing aggression.[4] The underlying cause of the behavior should be readily identified and handled accordingly. For instance, patients can become angry as a result of hallucinations, external provocation, or physical discomfort.

The Third-Person Approach

Although restraint may be necessary in emergency situations for patient and first responder safety, physical confrontation can usually be averted if de-escalation techniques are implemented before the patient gets out of control. De-escalation using a third-person approach, if implemented judiciously and cautiously by first responders, can be very effective in managing patients in the early stages of anger and aggression.

The third-person approach is similar to hostage crisis negotiation, in which a third party is brought in to negotiate a solution. Usually, it is much easier for the third person to take a neutral stance and to allow space for the angry person to step down. Billikopf postulates that all other things being equal, an outside third party has a greater chance than an insider of successfully mediating and resolving a difference.[6] The third person is not an arbiter trying to decide right from wrong, but a nonjudgmental facilitator of communication.

A "third party" or "third person" is a trained crisis interventionalist who was not present at the start of the dispute or conflict. A person who was involved in the conflict may be perceived, from the patient's standpoint, as being part of the problem. The ideal third person is someone who knows the patient well and with whom the patient has a certain degree of rapport.

The value of a therapeutic relationship has been a known and established fact for many decades. Research suggests that ineffective interpersonal relationships and interactions are major factors in escalating the aggressive behavior of a volatile individual.[8,9] Irwin concludes that intolerable environments and ineffectual interactions are far more likely to influence behaviors than are psychiatric symptoms alone.[10]

Use of the Third Person in De-escalation

Whenever an outburst is anticipated, the audience should be removed immediately. If team assistance is called in accordance with institutional policy, it may be better for the team members to stay in the background, ready to provide support when needed, but allow a single, third person from the care team to approach the patient. This less-than-expected response, or "under-reaction," can promote de-escalation.[11] The Pennsylvania Patient Safety Authority also suggests shifting the method of intervention from "a show of force to a show of support."[12] A 3-month study on the use of least restrictive interventions found that patients commonly select "verbal warning or talking things through" as the most valuable tool of anger management.[13] In short, the men (and women) in blue need to put their guns away and back off.  Crisis intervention teams will have greater success at de-escalating any situation, and there will be much less risk of injury to the patient and to law enforcement.

The third person should maintain a calm and supportive demeanor and use therapeutic communication skills. Avoid arguing with the patient or getting into a power struggle, and listen with empathy; the Greek Stoic philosopher Epictetus said that we have 2 ears and 1 mouth, so that we can speak less and listen more. In addition, state everything in clear, simple language: As anger escalates, the patient's perceptual field becomes limited; he or she probably cannot understand complex reasoning or process what you are saying. Tell the patient that you want to help, but he or she needs to calm down first. It is appropriate to say something like, "I would like to help you, but I can't hear you if you are screaming and yelling." Do not react to verbal attacks from the patient. Be aware of your own feelings of countertransference.

Staff members who take on the role of third person should have proper training in various techniques of nonviolent crisis intervention. The third person must also practice safety precautions, such as standing beyond arm's reach of the patient, positioning himself or herself for easy escape, and avoiding displays of body language that may be viewed as provocative to the patient.

Sometimes patients act out because they feel threatened. Assure the patient that he or she is safe, then set firm but nonthreatening limits. Offer choices to gain the patient's cooperation, and present positive reinforcement first. Positive reinforcement does not have to be a material reward; it can be praise and encouragement, or earning a certain privilege. In Rosenheck and Neale's 6-month study of 40 Veterans Affairs Assertive Community Treatment Program teams, clients with violent behavior who were exposed to negative limit-setting interventions typically had poorer outcomes.[14]

First responders have an obligation to maintain the safety of the patient and others in the environment. If restraint is deemed necessary, it should be used only when all measures of de-escalation have failed. In reality, no rigid policy or clinical guideline can spell out each and every scenario when physical restraint is the lesser of 2 evils. Crisis intervention workers have to rely on their own clinical judgment to weigh the risks and benefits of the measures they are considering. When to initiate physical restraint is a situation that depends on circumstances.[15]

References:

1. Weiss EM. Deadly restraint: a Hartford Courant investigative report. Hartford Courant. 1998;October 11-15. Section A.1 Available at" http://courant.ctnow.com/projects/restraint/data.stm

2. Stefan S. Legal and regulatory aspects of seclusion and restraint in mental health settings. Special edition: Violence and Coercion in Mental Health Settings: Eliminating the Use of Seclusion and Restraint. NTAC Networks. 2002;Summmer/Fall

3. Massachusetts Coalition for the Prevention of Medical Errors. Principles and Best Practice Recommendations to Improve Patient Safety Related to Restraint and Seclusion Use. 2003. Available at: http://www.macoalition.org/documents/RestraintPrinBestPrac-Definitions-Final.pdf Accessed on December 24, 2009.

4. Johnson B, Martin M, Guha M, Montgomery P. The experience of thought-disordered individuals preceding an aggressive incident. J Psychiatr Ment Health Nurs. 1997;4:213-220.

5. Davidson SE. The management of violence in general psychiatry. Advances in Psychiatric Treatment. 2005;11:362-370.

6. Billikopf G. Chapter 4: Interpersonal negotiation skills. In: Party-Directed Mediation: Helping Others Resolve Differences. Modesto, California: Regents of the University of California; 2009:85.

7. Peplau HE. Interpersonal Relations in Nursing. A Conceptual Frame of Reference for Psychodynamic Nursing. London: Macmillan; 1998.

8. Breeze J, Repper J. Struggling for control: the care experiences of “difficult” patients in mental health services. J Adv Nurs. 1998;28:1301-1311.

9. Secker J, Benson A, Balfe E, Lipsedge M, Robinson S, Walker J. Understanding the social context of violent and aggressive incidents on an inpatient unit. J Psychiatr Ment Health Nurs. 2004;11:172-178.

10. Irwin A. The nurse's role in the management of aggression. J Psychiatr Ment Health Nurs 2006;13:309-318.

11. Kreisberg L. Constructive Conflicts. Lanham, Md: Rowman & Littlefield; 1998:181-222

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