Methamphetamine-associated burn injuries: a retrospective analysis

Methamphetamine production and use has increased dramatically during the past 10 years. Methamphetamine production requires combining hazardous and volatile chemicals that expose the manufacturer to burn injuries from explosions and chemical spills. We sought to review the epidemiology of burn injuries in a rural burn center secondary to the use of amphetamine or methamphetamine and/or the manufacture of methamphetamine. Review of the records of 507 patients who were admitted to our burn unit from December 1, 1998, to December 31, 2001, revealed 34 patients who were involved in the use of amphetamines or methamphetamines and/or the manufacture of methamphetamine. Thirty-one patients tested positive for either amphetamine (n = 2) or methamphetamine (n = 29) on routine admission urine drug screens. Twenty of these patients were involved in the manufacture of methamphetamines. Three additional patients were identified as methamphetamine manufacturers but tested negative for the use of methamphetamines. The mean age of the study population was 31.88 +/- 7.65 years, with a male:female ratio of 10.3:1. The average burn size was 18.86 +/- 20.72, with the majority secondary to flame (n = 26). Patient burn admission histories were vague, and the patient's involvement in the manufacture of methamphetamine was often only later confirmed by media, the fire marshal, family members, or the patient. Fifteen patients showed the usual withdrawal pattern of agitation and hypersomnolence, with seven patients requiring detoxification with benzodiazepines. Two were admitted acutely to the psychiatric ward for uncontrollable agitation. Eighteen patients were offered chemical dependency treatment, and two completed therapy. There was one mortality. The mean cost per person was US 77,580 dollars (range, US 112 dollars - US 426,386 dollars). The increasing use of and manufacture of methamphetamine presents new challenges for the burn team because these patients can become violent and frequently need assistance with detoxification. Routine drug screens are mandatory in identifying methamphetamine use to alert burn unit personnel to particular management problems and target individuals who may be receptive to drug rehabilitation.     

Acute, transient urinary retention from combined ecstasy and methamphetamine use

Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are synthetic amphetamine analogs that have become increasingly popular, particularly among adolescents and young adults. Many deleterious physiologic effects arising from the use of these agents have been well documented in the medical literature. Urinary retention, however, has rarely been reported as an effect of MDMA or methamphetamine use and is thought to occur as a result of alpha-adrenoceptor stimulation of the bladder neck. We report a case of acute, transient urinary retention due to combined MDMA and methamphetamine use with laboratory confirmation.     

Methamphetamine abuse

Methamphetamine is a stimulant commonly abused in many parts of the United States. Most methamphetamine users are white men 18 to 25 years of age, but the highest usage rates have been found in native Hawaiians, persons of more than one race, Native Americans, and men who have sex with men. Methamphetamine use produces a rapid, pleasurable rush followed by euphoria, heightened attention, and increased energy. Possible adverse effects include myocardial infarction, stroke, seizures, rhabdomyolysis, cardiomyopathy, psychosis, and death. Chronic methamphetamine use is associated with neurologic and psychiatric symptoms and changes in physical appearance. High-risk sexual activity and transmission of human immunodeficiency virus are also associated with methamphetamine use. Use of methamphetamine in women who are pregnant can cause placental abruption, intrauterine growth retardation, and preterm birth, and there can be adverse consequences in children exposed to the drug. Treatment of methamphetamine intoxication is primarily supportive. Treatment of methamphetamine abuse is behavioral; cognitive behavior therapy, contingency management, and the Matrix Model may be effective. Pharmacologic treatments are under investigation.     

N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication

(+)- And (-)-amphetamine and methamphetamine were N-oxygenated by the cDNA expressed adult human flavin-containing monooxygenase form 3 (FMO3), their corresponding hydroxylamines. Two major polymorphic forms of human FMO3 were studied, and the results suggested preferential N-oxygenation by only one of the two enzymes. Chemically synthesized (+/-)-amphetamine hydroxylamine was also a substrate for the human FMO3 and it was converted to phenylpropanone oxime with a stereoselectivity ratio of trans/cis of 5:1. Human FMO3 also N-oxygenated methamphetamine to produce methamphetamine hydroxylamine. Methamphetamine hydroxylamine was also N-oxygenated by human FMO3, and the ultimate product observed was phenylpropanone. For amphetamine hydroxylamine, studies of the biochemical mechanism of product formation were consistent with the production of an N, N-dioxygenated intermediate that lead to phenylpropanone oxime. This was supported by the observation that alpha-deutero (+/-)-amphetamine hydroxylamine gave an inverse kinetic isotope effect on product formation in the presence of human FMO3. For methamphetamine, the data were consistent with a mechanism of human FMO3-mediated N,N-dioxygenation but the immediate product, a nitrone, rapidly hydrolyzed to phenylpropanone. The pharmacological activity of amphetamine hydroxylamine, phenylpropanone oxime, and methamphetamine hydroxylamine were examined for effects at the human dopamine, serotonin, and norepinephrine transporters. Amphetamine hydroxylamine and methamphetamine hydroxylamine were apparent substrates for the human biogenic amine transporters but phenylpropanone oxime was not. Presumably, phenylpropanone oxime or nitrone formation from amphetamine and methamphetamine, respectively, represents a detoxication process. Because of the potential toxic nature of amphetamine hydroxylamine and methamphetamine hydroxylamine metabolites and the polymorphic nature of N-oxygenation, human FMO3-mediated metabolism of amphetamine or methamphetamine may have clinical consequences.     

Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study

Patients with methamphetamine toxicity are presenting in greater numbers each year to emergency departments (ED) in the US. These patients are frequently agitated, violent, and often require physical and chemical restraint. The incidence and risk of rhabdomyolysis in this subpopulation is unknown. We conducted a 5-year retrospective review of all ED patients who received the final diagnosis of rhabdomyolysis. Patients with toxicology screens positive for methamphetamine were identified, and demographics, laboratory results, resource utilization, disposition, and outcome were compared to the remaining patients. Of the total 367 patients identified, 166 (43%) were toxicology positive for methamphetamine. Methamphetamine patients differed significantly from nonmethamphetamine patients with regard to demographics and hospital utilization. Methamphetamine patients had significantly higher mean initial creatine phosphokinase (CK), 12,439 U/L versus 5,678 U/L (P = 0.02), and lower mean peak CK, 16,827 U/L versus 19,426 U/L (P = 0.03). The development of acute renal failure was not significantly different between the 2 groups. There were 16 total deaths in the study population, 11 from concomitant infection/sepsis. An association between methamphetamine abuse and rhabdomyolysis may exist, and CK should be measured in the ED as a screen for potential muscle injury in this subpopulation. Patients with rhabdomyolysis with an unclear cause should be screened for methamphetamine or other illicit drugs.     

Delayed ischemic stroke associated with methamphetamine use

A 19-year-old woman had right occipital infarction 3 months after she had injected methamphetamine. No other possible causes of stroke could be found in this case. Magnetic resonance angiography revealed beading of the right posterior cerebral artery, which suggested vasculitis. Her symptoms were right-sided headache, left superior quadrant hemianopia, and left hypesthesia, which gradually improved without any treatment. Methamphetamine has been known to cause hemorrhagic and ischemic stroke relatively soon after administration. We report here that methamphetamine may also cause chronic cerebral vasculitis and delayed ischemic stroke.     

Single-reagent polarization fluoroimmunoassay of methamphetamine in urine

We developed a polarization fluoroimmunoassay for the specific detection of methamphetamine in urine. Sheep antiserum raised against methamphetamine was premixed with a fluorescein-labeled amphetamine tracer in a single reagent. The use of labeled amphetamine gave a more sensitive and more specific assay than did the use of a labeled methamphetamine tracer. The assay system had equal sensitivity for the d- and l-isomers of methamphetamine while the cross reactivity of amphetamine and other structurally related compounds was 3% or less. With a positive/negative cutoff concentration set at 1 mg/L, the polarization fluoroimmunoassay reliably identified human urines that had been reported positive for methamphetamine by an established gas-liquid chromatographic method.     

Crystal Methamphetamine‐Associated Cardiomyopathy: Tip of the Iceberg?

Abstract

Background.?Crystal methamphetamine has become a drug of widespread use. Previous reports describe myocardial infarction, pulmonary edema, and aortic dissection related to methamphetamine use. Cardiomyopathy due to methamphetamine exposure has been rarely described. Methods.?We identified 1640 patients admitted in a 4‐yr period with a primary or secondary diagnosis of cardiomyopathy. We excluded patients with known cause of cardiomyopathy other than substance abuse. We found 120 patients had a diagnosis of substance abuse, including 21 patients with methamphetamine use. We retrospectively reviewed the medical records of these 21 crystal methamphetamine users. Results.?Nineteen (84%) underwent echocardiography with consistent findings of dilated cardiomyopathy and global ventricular dysfunction. Of five who had a nuclear myocardial perfusion study, none had evidence of ischemia or infarct. Of six who underwent cardiac catheterization, only one had evidence of coronary stenosis. Conclusion.?Methamphetamine use appears to produce cardiomyopathy in some users. The pathogenesis is probably similar to that of cocaine and catecholamine‐induced cardiomyopathy. Cellular, animal, and clinical data support the link between methamphetamine exposure and myocardial pathology.     

The bioavailability of intranasal and smoked methamphetamine

BACKGROUND: Patients in harm-reduction treatment programs are switching from intravenous to other routes of methamphetamine (INN, metamfetamine) administration to avoid risks associated with needle use. Relatively little has been reported about the bioavailability of methamphetamine when smoked or used intranasally. METHODS: Eight experienced methamphetamine users were administered smoked or intranasal methamphetamine concurrently with an intravenous dose of deuterium-labeled methamphetamine. Plasma and urine concentrations were measured for calculation of bioavailability and other pharmacokinetic parameters by noncompartmental methods. RESULTS: Methamphetamine was well absorbed after smoking or intranasal administration, with bioavailabilities of 79% after intranasal administration and 67% of the estimated delivered dose or 37.4% of the absolute (pipe) dose after smoking. Maximum methamphetamine concentrations occurred at 2.7 and 2.5 hours after intranasal and smoked doses. The elimination half-life was similar for intravenous (11.4 hours), intranasal (10.7 hours), and smoked (10.7 hours) methamphetamine. Clearance (272 mL x h(-1) x kg(-1)), steady-state volume of distribution (4.2 L/kg), and mean residence time (16 hours) of the intravenous dose were similar to previously reported values. Dextroamphetamine (INN, dexamfetamine) half-life (all routes) was 16.2 hours. Methamphetamine and dextroamphetamine renal clearances (all routes) were about 100 and 1100 mL x h(-1) x kg(-1), respectively. CONCLUSIONS: Intranasal and smoked methamphetamine are well absorbed. Although intranasal or smoked routes may decrease the risk of transmission of blood-borne diseases, exposure to methamphetamine and the possibility of drug-related complications remain substantial.     

Prothrombotic gene variation and new vascular events after cerebral ischemia of arterial origin

Summary. Background: Several genetic variants involved in hemostasis have been associated with ischemic stroke or myocardial infarction (MI). Stroke patients who carry a prothrombotic genotype may also be at increased risk for subsequent vascular events. Patients and methods: We included 887 patients with non‐disabling cerebral ischemia of arterial origin, who were referred to the University Medical Center Utrecht in the Netherlands between 1995 and 2005 and followed them for the occurrence of ischemic stroke, MI or death. The primary outcome was a composite of death from all vascular causes, non‐fatal ischemic stroke, non‐fatal MI, whichever happened first. We selected 22 prothrombotic variants in 14 genes that were previously associated with ischemic stroke or MI or had evidence of functionality. Results: During a 4.6‐year mean follow‐up period new vascular events occurred in 135 patients (annual event rate 3.3%). None of the 22 variants was associated with the occurrence of new vascular events. Eight additional analyses with secondary outcomes or among subgroups revealed four associations that were likely to be false positive after accounting for multiple testing. Conclusions: In this cohort, prothrombotic genetic variants do not affect the risk of new vascular events after cerebral ischemia of arterial origin. This study does not support the use of prothrombotic genetic variants to identify stroke patients at increased risk for new vascular events or to guide antithrombotic treatment.     

Methamphetamine-related Psychiatric Visits to an Urban Academic Emergency Department: An Observational Study

Background

Methamphetamine, a stimulant of abuse, is associated with a significant number of Emergency Department (ED) visits. Methamphetamine use may produce psychiatric symptoms including acute psychosis, depression, and anxiety disorders.

Study Objectives

To characterize psychiatric emergencies either directly or indirectly attributable to methamphetamine use in an urban academic ED.

Methods

We analyzed a database of patients determined to have an ED visit that was either methamphetamine related or non-methamphetamine related. We retrospectively reviewed the records of the subset of ED visits from this database with psychiatric diagnoses. We compared the characteristics of patients with methamphetamine-related psychiatric visits (MRPVs) and non-methamphetamine-related psychiatric visits (non-MRPVs).

Results

We identified 130 patients with MRPVs. This represented 7.6% (130 of 1709) of all psychiatric visits. Patients with MRPV, compared to non-MRPV patients, were younger (34.4 years vs. 39.1 years, respectively, p = 0.0005), more likely to be uninsured (55% vs. 37%, respectively, p = 0.001), and less likely to have a past history of depression (10% vs. 19%, respectively, p = 0.011). Many characteristics between the two groups (MRPV vs. non-MRPV) were similar: likelihood of patient being placed on a psychiatric hold; hospital charges; previous histories of psychiatric visits; and history of anxiety, bipolar disorder, or schizophrenia.

Conclusions

Methamphetamine may be related to a significant proportion (7.6%) of psychiatric ED visits. Furthermore, patients with methamphetamine-associated psychiatric visits are younger, have lower rates of depression, are more likely to be uninsured, and are less likely to have a substance abuse-related chief complaint than patients with non-methamphetamine-associated ED psychiatric visits.     

Newest aspects on the association between migraine and cardiovascular disease: The role of modifying factors

Migraine has been established as a risk factor for ischemic stroke. Further evidence suggests that migraine is also associated with other ischemic vascular events, including myocardial infarction and cardiovascular death. However, these associations appear to be limited to the subgroup of patients with migraine with aura (MA). Moreover, there is increasing evidence that among patients with MA, additional subgroups exist that carry particular increased risk. The association with ischemic stroke is, for example, particularly strong for younger women with MA who smoke and/or use oral contraceptives. Results from recent studies support an even more complex interrelationship characterized by additional modifying effects of other factors on the association between MA and ischemic vascular events. These include vascular risk factors, migraine attack frequency, and genetic variants. In addition, there appear to be differential effects with regard to ischemic stroke and myocardial infarction. These new findings await confirmation in independent patient populations and are currently not sufficient to argue for a change in diagnostic testing or treatment.     

Association of methamphetamine use and restrictive interventions in an acute adult inpatient mental health unit: A retrospective cohort study

The aim of the present study was to describe incidences of restrictive interventions and the association of methamphetamine use at an acute adult inpatient mental health unit in metropolitan Melbourne, Victoria, Australia. A total of 232 consecutive consumer admissions to the inpatient unit across a 3‐month period were described for illicit substance use and the use of restrictive interventions (seclusion, mechanical restraint, and physical restraint) prior to and during admission. Of all admissions, 25 (10.8%) involved consumers subjected to a restrictive intervention. Methamphetamine use was either self‐reported or detected by saliva test for 71 (30.6%) consumers. Following multivariate analyses, methamphetamine use (odds ratio (OR): 7.83, 95% confidence interval (CI): 2.33–26.31) and restrictive intervention in the emergency department prior to admission (OR: 8.85, 95% CI: 2.83–27.70) were significant independent predictors of the use of restrictive interventions after inpatient admission. Anecdotal observations provided by clinical mental health staff that consumers intoxicated with methamphetamine appear to require restrictive intervention more frequently than other consumers was confirmed with the results of the current study. As the state of Victoria in Australia is on a pathway to the elimination of the use of restrictive interventions in mental health services, clinicians need to develop management strategies that provide specialist mental health care using the least‐restrictive interventions. Although 26.8% of methamphetamine users were secluded after admission, restrictive interventions should not be the default management strategy for consumers who present with self‐report or positive screen for methamphetamine use.     

Prevalence and Risk Factors of Emergency Department Presentations with Methamphetamine Intoxication or Dependence: A Systematic Review and Meta-analysis

Background: Methamphetamine intoxication presentations to emergency departments (EDs) including trauma centres, general EDs and psychiatric emergency services have risen world-wide. Objectives: A review of the clinical characteristics of patients presenting to a trauma centre or ED with methamphetamine intoxication or dependence to aid development of health service policy and training for health personnel. Methods: PubMed, PsycINFO, CINAHL and Scopus (1990–2017) were searched. A systematic review of all clinical characteristics was conducted, and a meta-analysis undertaken for variables with standard measures (prevalence, age, gender); 23 studies met the inclusion criteria of which 17 could be used in the meta-analysis. Results: Methamphetamine-related presentations were characterised by cardiac complications, psychiatric symptoms and aggression with safety risk to health personnel. The pooled prevalence of methamphetamine positive cases in emergency settings was higher in studies using toxicology analysis to determine methamphetamine use (8 studies, 22.8% 95% CI 15.4–32.5) compared to self-reporting (9 studies 5.7%, 95% CI 2.8–11.2, Q?=?12.42, p?<?0.001). Pooled variance of methamphetamine positive cases was 57.1% in men and 42.9% in women. The mean age of those who were methamphetamine positive was 28.4?years and for those methamphetamine negative cases it was 38.4?years. Conclusions: In this review, we found a higher prevalence of methamphetamine use amongst males and in the younger demographic. Targeted training programmes for frontline staff and management approaches for prompt multi-disciplinary service engagement are recommended as well as appropriate resourcing, such as mental health staff in EDs or mental health beds to accommodate this subgroup of the patient cohort.     

Fat-mobilizing action of amphetamine

The effects of amphetamine and methamphetamine on plasma free fatty acid (FFA), blood glucose, serum total fat, and triglyceride concentrations were investigated in 21 subjects; the effect of epinephrine were studied in an identical manner in 14 subjects.The administration of amphetamine and methamphetamine led to an increase in the plasma FFA concentration. No significant changes were found in the blood glucose, serum total fat, and triglyceride concentrations.Kinetic studies of FFA were also made in some of the subjects receiving amphetamine, methamphetamine, and epinephrine. It was shown that amphetamine and methamphetamine lead to an augmentation of plasma FFA pool due to a primary increase of FFA production rate.Catecholamine depletion, by prolonged parenteral adminstration of reserpine, nearly completely abolished the adipokinetic action of amphetamine whereas the effect of epinephrine was greatly potentiated. This was interpreted as evidence for the dependence of the adipokinetic action of amphetamine on endogenous catecholamines.ESTIMATED FROM A DOSE RATIO (AMPHETAMINE: epinephrine) of 352:1, the relative adipokinetic potency of amphetamine, expressed as peak DeltaFFA rise, +DeltaFFA area, and DeltaFFA production rate, respectively, was found to be 55, 84, and 39% in comparison with the same effects of epinephrine. The more pronounced changes in +DeltaFFA area reflect the longer duration of action of amphetamine viz. epinephrine.This study demonstrates that amphetamine is an adipokinetic agent causing an increase in the plasma FFA pool of a lesser extent but of longer duration than equipressor doses of epinephrine. The mechanism of fat-mobilizing action of amphetamine is indirect i.e., dependent on endogenous catecholamine release.     

Efficacy of the Marlatt cognitive-behavioral model on decreasing relapse and craving in women with methamphetamine dependence: A clinical trial

Methamphetamine use is now a global concern, which warrants a thorough assessment of the effectiveness of its different treatment modalities. To evaluate the efficacy of the Marlatt cognitive-behavioral model on decreasing the rate of relapse and craving in women with methamphetamine dependence, we conducted the present quasi-experimental study with a pretest–posttest and control group design in which 80 women with methamphetamine dependence who referred to Farabi Hospital of Kermanshah were chosen through convenience sampling and randomly allocated to two groups of intervention and control. Before and after the intervention, the members of both groups completed the Craving Belief Questionnaire (by Clark and Beck) and the Desire for Drug Questionnaire (by Franklin et al.). The results showed that in the intervention group, the Marlatt cognitive-behavioral treatment led to decreased relapse and craving. Cognitive-behavioral therapy can, therefore, be a treatment option to diminish relapse and craving in individuals with methamphetamine dependence.     

Amphetamine‐type stimulant use among patients admitted to the emergency department behavioural assessment unit: Screening and referral outcomes

Amphetamine‐type stimulant use, including methamphetamine, amphetamine, and 3,4‐methylenedioxymethamphetamine, is associated with a range of behavioural symptoms. Screening for amphetamine‐type stimulant use among people presenting to the emergency department with behavioural disturbance and referral to treatment has not been evaluated. The objective of this study was to determine the prevalence of amphetamine‐type stimulant use among patients admitted to a behavioural assessment unit and report referral outcomes. A prospective observational design was used. Individuals who tested positive or self‐reported amphetamine‐type stimulant use were referred to the alcohol and other drug clinician. We measured the prevalence of amphetamine‐type stimulant use in saliva and by self‐report along with rates of referral. The setting was a behavioural assessment unit located within an Australian emergency department. Admitted adults were enrolled from July to December 2017. Those who tested positive or self‐reported amphetamine‐type stimulant use were provided with harm reduction advice and offered referral. Four hundred and seventy‐two tests were performed. Fifteen were excluded due to invalid results or redundant enrolment. Of the 457 individuals, 59% were male, with a mean age of 35 years (SD 13). Fifty‐three (11.6%, 95% CI: 8.9–15.0) tested positive for amphetamine‐type stimulants. Of those with a negative test, 44 (9.6%, 95% CI: 7.3–12.7) self‐reported amphetamine‐type stimulant use in the previous 24 hours. The prevalence of amphetamine‐type stimulant use was 21.2% (95% CI: 17.7–25.2). Most accepted referral to the alcohol and other drug clinician (85.6%, 95% CI 77.2–91.2). The emergency visit represents a window of opportunity for screening for amphetamine‐type stimulant use and initiating referrals.     

Secondary prevention of stroke

Patients suffering a transient ischaemic attack (TIA) or ischaemic stroke (IS) have a high recurrence risk. Secondary prevention aims to prevent not only further strokes but also cardiac events. Important parts of secondary prevention regimens are the modification of vascular risk factors and the inhibition of platelet function or anticoagulation if indicated. The inhibition of platelet function is effective in the reduction of secondary vascular events in patients with TIA or stroke. This is true for acetylsalicylic acid (ASA), clopidogrel, and the combination of ASA plus slow-release dipyridamole. A prediction model which allows to identify patients in whom clopidogrel or dipyridamol plus ASA is superior to ASA for the secondary prevention of stroke is presented.