麻酔薬および麻酔関連薬使用ガイドライン 第3版 Ⅱ 鎮痛薬・拮抗薬.
Addis A, Moretti ME, Ahmed Syed F, Einarson TR, Koren G.
Fetal effects of cocaine: an updated meta-analysis.
Reprod Toxicol. 2001 Jul-Aug;15(4):341-69. doi: 10.1016/s0890-6238(01)00136-8.
Abstract/Text
BACKGROUND: A very large number of women in the reproductive age group consume cocaine, leading to grave concerns regarding the long term health of millions of children after in utero exposure. The results of controlled studies have been contradictory, leading to confusion, and, possible, misinformation and misperception of teratogenic risk.
OBJECTIVE: To systematically review available data on pregnancy outcome when the mother consumed cocaine.
METHODS: A meta-analysis of all epidemiologic studies based on a priori criteria was conducted. Comparisons of adverse events in subgroups of exposed vs. unexposed children were performed. Analyses were based on several exposure groups: mainly cocaine, cocaine plus polydrug, polydrug but no cocaine, and drug free.
RESULTS: Thirty three studies met our inclusion criteria. For all end points of interest (rates of major malformations, low birth weight, prematurity, placental abruption, premature rupture of membrane [PROM], and mean birth weight, length and head circumference), cocaine-exposed infants had higher risks than children of women not exposed to any drug. However, most of these adverse effects were nullified when cocaine exposed children were compared to children exposed to polydrug but no cocaine. Only the risk of placental abruption and premature rupture of membranes were statistically associated with cocaine use itself.
CONCLUSIONS: Many of the perinatal adverse effects commonly attributed to cocaine may be caused by the multiple confounders that can occur in a cocaine using mother. Only the risk for placental abruption and PROM could be statistically related to cocaine. For other adverse effects, additional studies will be needed to ensure adequate statistical power.
Zimmerman JL.
Cocaine intoxication.
Crit Care Clin. 2012 Oct;28(4):517-26. doi: 10.1016/j.ccc.2012.07.003. Epub 2012 Aug 30.
Abstract/Text
Cocaine, a natural alkaloid derived from the coca plant, is one of the most commonly abused illicit drugs. Cocaine is commonly abused by inhalation, nasal insufflation, and intravenous injection, resulting in many adverse effects that ensue from local anesthetic, vasoconstrictive, sympathomimetic, psychoactive, and prothrombotic mechanisms. Cocaine can affect all body systems and the clinical presentation may primarily result from organ toxicity. Among the most severe complications are seizures, hemorrhagic and ischemic strokes, myocardial infarction, aortic dissection, rhabdomyolysis, mesenteric ischemia, acute renal injury and multiple organ failure.
Copyright © 2012 Elsevier Inc. All rights reserved.
Moeller KE, Lee KC, Kissack JC.
Urine drug screening: practical guide for clinicians.
Mayo Clin Proc. 2008 Jan;83(1):66-76. doi: 10.4065/83.1.66.
Abstract/Text
Drug testing, commonly used in health care, workplace, and criminal settings, has become widespread during the past decade. Urine drug screens have been the most common method for analysis because of ease of sampling. The simplicity of use and access to rapid results have increased demand for and use of immunoassays; however, these assays are not perfect. False-positive results of immunoassays can lead to serious medical or social consequences if results are not confirmed by secondary analysis, such as gas chromatography-mass spectrometry. The Department of Health and Human Services' guidelines for the workplace require testing for the following 5 substances: amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. This article discusses potential false-positive results and false-negative results that occur with immunoassays of these substances and with alcohol, benzodiazepines, and tricyclic antidepressants. Other pitfalls, such as adulteration, substitution, and dilution of urine samples, are discussed. Pragmatic concepts summarized in this article should minimize the potential risks of misinterpreting urine drug screens.
Traub SJ, Hoffman RS, Nelson LS.
Body packing--the internal concealment of illicit drugs.
N Engl J Med. 2003 Dec 25;349(26):2519-26. doi: 10.1056/NEJMra022719.
Abstract/Text
Weber JE, Chudnofsky CR, Boczar M, Boyer EW, Wilkerson MD, Hollander JE.
Cocaine-associated chest pain: how common is myocardial infarction?
Acad Emerg Med. 2000 Aug;7(8):873-7. doi: 10.1111/j.1553-2712.2000.tb02064.x.
Abstract/Text
OBJECTIVE: Prior studies addressing the incidence of acute myocardial infarction (AMI) in patients with cocaine-associated chest pain have found divergent results. Previous prospective studies, which found approximately a 6% incidence of AMI, have been criticized for selection bias. This study sought to determine the rate of AMI in patients with cocaine-associated chest pain.
METHODS: All patients seen in an urban university-affiliated hospital between July 1996 and February 1998 were identified by ICD-9 medical records search for cocaine use and chest pain/ acute coronary syndromes. In this system, all faculty admit all patients with cocaine-associated chest pain for at least 23-hour observation periods. Data collected included demographics, medical and cocaine use history, presenting characteristics, hospital course, cardiovascular complications, and diagnostic tests using a 119-item closed-question data instrument with high interrater reliability. The main outcome measure was AMI according to World Health Organization (WHO) criteria.
RESULTS: There were 250 patients identified with a mean age of 33.5 +/- 8.5 years; 77% were male; 84% were African American. Of 196 patients tested, 185 had cocaine or cocaine metabolites in the urine (94%). The incidence of cardiac risk factors were: hypercholesterolemia, 8%; diabetes, 6%; family history, 34%; hypertension, 26%; tobacco use, 77%; prior MI, 6%; and prior chest pain, 40%. Seventy-seven percent admitted to cocaine use in the preceding 24 hours: crack, 85%; IV, 2%; nasal, 6%. Twenty-five patients (10%) had electrocardiographic evidence of ischemia. A total of 15 patients experienced an AMI (6%; 95% CI = 4.1% to 8.9%) using WHO criteria. Complications were infrequent: bradydysrrhythmias, 0.4%; congestive heart failure, 0.4%; supraventricular tachycardia, 1.2%; sustained ventricular tachycardia, 0.8%.
CONCLUSION: The incidence of AMI was 6% in patients with cocaine-associated chest pain. This result is identical to that found in prior prospective studies.
Schwartz BG, Rezkalla S, Kloner RA.
Cardiovascular effects of cocaine.
Circulation. 2010 Dec 14;122(24):2558-69. doi: 10.1161/CIRCULATIONAHA.110.940569.
Abstract/Text
Tomaszewski C, McKinney P, Phillips S, Brent J, Kulig K.
Prevention of toxicity from oral cocaine by activated charcoal in mice.
Ann Emerg Med. 1993 Dec;22(12):1804-6. doi: 10.1016/s0196-0644(05)80404-4.
Abstract/Text
STUDY OBJECTIVE: To study the effectiveness of activated charcoal in preventing toxicity after an enterally administered cocaine hydrochloride overdose in mice.
DESIGN: A prospective, randomized, controlled animal laboratory investigation.
INTERVENTIONS: Fasted mice were given aqueous cocaine hydrochloride (0.8% final concentration) 100 mg/kg body weight orally by gavage tube. One minute later, animals received one of three treatments by gavage: 1 g activated charcoal/kg body weight, 2 g activated charcoal/kg body weight, or an equivolume of water (control). All treatments consisted of 20 mL/kg body weight of an activated charcoal slurry with water.
MEASUREMENTS: After 24-hour observation, proportions of seizures and deaths between each group were compared using Pearson chi 2 test followed by Fisher's exact test (P < .017 for significance after Bonferroni's correction).
MAIN RESULTS: There were 20 seizures and 16 deaths in the control group (20 mice). There were four seizures (P = .0004) and one death (P = .0004) in the 1-g activated charcoal/kg group (ten mice) and five seizures (P = .0018) and three deaths (P = .015) in the 2-g activated charcoal/kg group (ten mice).
CONCLUSION: In this mouse model, activated charcoal decreased the incidence of seizures and death after an enteral cocaine hydrochloride overdose.
Hind CR.
Pulmonary complications of intravenous drug misuse. 1. Epidemiology and non-infective complications.
Thorax. 1990 Nov;45(11):891-8. doi: 10.1136/thx.45.11.891.
Abstract/Text
Ricaurte GA, Finnegan KT, Irwin I, Langston JW.
Aminergic metabolites in cerebrospinal fluid of humans previously exposed to MDMA: preliminary observations.
Ann N Y Acad Sci. 1990;600:699-708; discussion 708-10. doi: 10.1111/j.1749-6632.1990.tb16919.x.
Abstract/Text
Rosenberg J, Pentel P, Pond S, Benowitz N, Olson K.
Hyperthermia associated with drug intoxication.
Crit Care Med. 1986 Nov;14(11):964-9. doi: 10.1097/00003246-198611000-00011.
Abstract/Text
Hyperthermia (temperature of at least 40.5 degrees C for at least one hour) associated with drug intoxication was identified in 12 patients over a 5-yr period. Intoxication was due to anticholinergic drugs (tricyclic antidepressants, antipsychotics, antihistamines), CNS stimulants (phencyclidine, cocaine, 3,4-methylene dioxyamphetamine, mescaline, lysergic acid diethylamide), salicylates, or combinations of these. Hyperthermia was present in four patients on admission, but its onset was delayed up to 12 h in the remainder. Outcome of hyperthermic patients was poor: five died and four had severe permanent neurologic sequelae. Clinical signs common to patients who developed hyperthermia were increased muscular activity and absence of sweating. Five patients suffered seizures, and four did not respond to anticonvulsant medication until body temperature was lowered. Cooling did not appear to favorably affect the outcome after body temperature had remained above 40.5 degrees C for a prolonged period. Prevention of death or neurologic sequelae from drug-induced hyperthermia depends upon the recognition of risk factors and the prompt treatment of hyperthermia.
Rao RB, Hoffman RS：Chapter 152: Cocaine and Other Sympathomimetics. Rosen’s Emergency Medicine, 7th ed.Marx J, et al. eds.,Mosby, 2009.
Duberstein JL, Kaufman DM.
A clinical study of an epidemic of heroin intoxication and heroin-induced pulmonary edema.
Am J Med. 1971 Dec;51(6):704-14. doi: 10.1016/0002-9343(71)90298-1.
Abstract/Text
Frand UI, Shim CS, Williams MH Jr.
Methadone-induced pulmonary edema.
Ann Intern Med. 1972 Jun;76(6):975-9. doi: 10.7326/0003-4819-76-6-975.
Abstract/Text
Mills CA, Flacke JW, Flacke WE, Bloor BC, Liu MD.
Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine.
Can J Anaesth. 1990 Mar;37(2):238-44. doi: 10.1007/BF03005476.
Abstract/Text
Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lange RA, Cigarroa RG, Flores ED, McBride W, Kim AS, Wells PJ, Bedotto JB, Danziger RS, Hillis LD.
Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade.
Ann Intern Med. 1990 Jun 15;112(12):897-903. doi: 10.7326/0003-4819-112-12-897.
Abstract/Text
STUDY OBJECTIVE: To determine whether beta-adrenergic blockade augments cocaine-induced coronary artery vasoconstriction.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: A cardiac catheterization laboratory in an urban teaching hospital.
PATIENTS: Thirty clinically stable patient volunteers referred for catheterization for evaluation of chest pain.
INTERVENTIONS: Heart rate, arterial pressure, coronary sinus blood flow (by thermodilution), and epicardial left coronary arterial dimensions were measured before and 15 minutes after intranasal saline or cocaine administration (2 mg/kg body weight) and again after intracoronary propranolol administration (2 mg in 5 minutes).
MEASUREMENTS AND MAIN RESULTS: No variables changed after saline administration. After cocaine administration, arterial pressure and rate-pressure product increased; coronary sinus blood flow fell (139 +/- 28 [mean +/- SE] to 120 +/- 20 mL/min); coronary vascular resistance (mean arterial pressure divided by coronary sinus blood flow) rose (0.87 +/- 0.10 to 1.05 +/- 0.10 mm Hg/mL.min); and coronary arterial diameters decreased by between 6% and 9% (P less than 0.05 for all variables). Subsequently, intracoronary propranolol administration caused no change in arterial pressure or rate-pressure product but further decreased coronary sinus blood flow (to 100 +/- 14 mL/min) and increased coronary vascular resistance (to 1.20 +/- 0.12 mm Hg/mL.min) (P less than 0.05 for both).
CONCLUSIONS: Cocaine-induced coronary vasoconstriction is potentiated by beta-adrenergic blockade. Beta-adrenergic blocking agents probably should be avoided in patients with cocaine-associated myocardial ischemia or infarction.
Hollander JE.
Cocaine intoxication and hypertension.
Ann Emerg Med. 2008 Mar;51(3 Suppl):S18-20. doi: 10.1016/j.annemergmed.2007.11.008. Epub 2008 Jan 11.
Abstract/Text
Lange RA, Hillis LD.
Cardiovascular complications of cocaine use.
N Engl J Med. 2001 Aug 2;345(5):351-8. doi: 10.1056/NEJM200108023450507.
Abstract/Text
Honderick T, Williams D, Seaberg D, Wears R.
A prospective, randomized, controlled trial of benzodiazepines and nitroglycerine or nitroglycerine alone in the treatment of cocaine-associated acute coronary syndromes.
Am J Emerg Med. 2003 Jan;21(1):39-42. doi: 10.1053/ajem.2003.50010.
Abstract/Text
The purpose of the present study was to compare the use of lorazepam plus nitroglycerine (NTG) versus NTG alone in the reduction of cocaine induced chest pain in the emergency department. The secondary objective of the study was to help determine the safety of lorazepam in the treatment of cocaine- associated chest pain. The study was a prospective, randomized, single-blinded, controlled trial conducted at an university-affiliated urban emergency department (ED). All patients who presented with cocaine-associated chest pain were enrolled. Exclusion criteria included age greater than 45 years, documented coronary artery disease, chest pain of more than 72 hours duration, or pretreatment with nitroglycerin. Patients were given either sublingual nitroglycerine (SL NTG) (Group 1) or SL NTG plus 1 mg of lorazepam intravenously (Group 2) every 5 minutes for a total of 2 doses. Chest pain was recorded on an ordinal scale of 0 to 10 at baseline, and then at 5 minutes after each dose. Adverse reactions to medication were also recorded. Twenty-seven patients met the inclusion criteria and were enrolled in the study. The average age of these subjects was 34.1 years, and 67% were men. The NTG-only group consisted of 15 patients and the NTG-plus-lorazepam group consisted of 12 patients. Baseline mean chest-pain scores were 6.87 in Group 1 and 6.54 in Group 2, with no differences between groups. Five minutes after initial treatment, mean scores for the two groups were 5.2 and 3.9, respectively, with a difference in means of 1.24 (95% confidence interval [CI] -0.8-3.8). Five minutes after the second treatment, the mean scores were 4.6 and 1.5, respectively, with a difference in means of 3.1 (95% CI 1.2-5). Kruskal-Wallis testing showed a significant difference in pain relief between the two study groups (P =.003), with greater pain relief noted at 5 and 10 minutes in the NTG-plus-lorazepam group (P =.02 and P =.005, respectively). All patients in the study were admitted to the hospital, but no patient in either group had an acute myocardial infarction or cardiac complications in the ED. No adverse side effects were noted for either group. The early use of lorazepam with NTG was more efficacious than NTG alone, and appears to be safe in relieving cocaine-associated chest pain.
Copyright 2003, Elsevier Science (USA). All rights reserved.)
Baumann BM, Perrone J, Hornig SE, Shofer FS, Hollander JE.
Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes.
Acad Emerg Med. 2000 Aug;7(8):878-85. doi: 10.1111/j.1553-2712.2000.tb02065.x.
Abstract/Text
INTRODUCTION: To the authors' knowledge, treatment of patients with cocaine-associated acute coronary syndromes has not been rigorously investigated in symptomatic patients.
OBJECTIVE: To perform a randomized double-blind trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes.
METHODS: Patients with potential cocaine-associated acute coronary syndromes were randomized to treatment with either diazepam, nitroglycerin, or both every 5 minutes or until symptom resolution. Outcomes were chest pain resolution (measured by visual analog scale), and changes in blood pressure, pulse rate, cardiac output (L/min), cardiac index (L/min/m2), stroke volume (mL/beat), and stroke index (mL/beat/m2) over the 15-minute treatment period. To adjust for seven outcomes using the Bonferroni correction, alpha was set at 0.007.
RESULTS: Forty patients were enrolled (diazepam, 12; nitroglycerin, 13; both, 15). Patients had a mean age (+/-SD) of 35.4 (+/-7.5) years; 75% were male. They presented a mean of 5 hours and 37 minutes after cocaine use. Baseline demographics, cocaine use patterns, chest pain characteristics, and initial electrocardiograms were similar for all groups. Chest pain severity improved similarly in the three groups [-33.3 mm (+/-8.0); -30.7 mm (+/-7.1); -33.0 mm (+/-7.9); p = 0.6]. The stroke index decreased during the 15-minute treatment period for all groups (diazepam, -8.7 (+/-3.3); nitroglycerin, -3.1 +/- 2.8; both, -1.8 (+/-3.1) mL/beat/m2; p = 0.03). After adjustment for differences between baseline hemodynamic and cardiac profiles and multiple comparisons, there was no difference in any response to therapy over time for the different treatments.
CONCLUSIONS: For treatment of patients with potential cocaine-associated acute coronary syndromes, chest pain resolutions and changes in cardiac performance are not different in patients treated with diazepam or nitroglycerin. In this study, the use of both agents did not offer any advantage over either agent alone.
Crandall CG, Vongpatanasin W, Victor RG.
Mechanism of cocaine-induced hyperthermia in humans.
Ann Intern Med. 2002 Jun 4;136(11):785-91. doi: 10.7326/0003-4819-136-11-200206040-00006.
Abstract/Text
BACKGROUND: The lethal effects of cocaine are unique among those of other illicit drugs because cocaine has the propensity to cause hyperthermia. The traditional view is that cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregulatory adjustments that mediate heat dissipation.
OBJECTIVE: To test the effects of cocaine on body temperature regulation in humans.
DESIGN: Randomized, double-blind, placebo-controlled crossover trial.
SETTING: A cardiovascular physiology laboratory in Dallas, Texas.
PARTICIPANTS: 7 healthy, cocaine-naive volunteers.
INTERVENTION: Progressive passive heat stress, during which each participant received intranasal cocaine (2 mg/kg of body weight) or placebo (lidocaine, 2 mg/kg).
MEASUREMENTS: Esophageal temperature, skin blood flow, sweat rate, and perceived thermal sensation.
RESULTS: Three major new findings were noted. First, cocaine substantially augmented the progressive increase in esophageal temperature during heat stress (P < 0.001). Second, this augmentation was explained by a rightward shift in the esophageal temperature threshold for the onset of both cutaneous vasodilation (37.37 +/- 0.09 degrees C for cocaine vs. 37.06 +/- 0.07 degrees C for lidocaine; P = 0.01) and sweating (37.38 +/- 0.09 degrees C for cocaine vs. 37.07 +/- 0.06 degrees C for lidocaine; P = 0.002). Third, cocaine paradoxically impaired the perception of heating by attenuating the progressive increase in thermal discomfort associated with heat stress.
CONCLUSIONS: In humans, impaired heat dissipation is a major mechanism by which cocaine elevates body temperature. When healthy, cocaine-naive persons are subjected to passive heating, pretreatment with even a small dose of intranasal cocaine impairs sweating and cutaneous vasodilation (the major autonomic adjustments to thermal stress) and heat perception (the key trigger for behavioral adjustments).
Catravas JD, Waters IW.
Acute cocaine intoxication in the conscious dog: studies on the mechanism of lethality.
J Pharmacol Exp Ther. 1981 May;217(2):350-6.
Abstract/Text
