Use of clonidine in the prevention and management of neonatal abstinence syndrome.

INTRODUCTION: Neonatal abstinence syndrome (NAS) is a complicated medical condition with treatment regimens that traditionally have included methadone and other opioids, barbiturates, and benzodiazepines. We describe a case series in which clonidine was used for the prevention and management of patients with NAS. PATIENTS AND METHODS: Medical records of infants treated with clonidine for NAS from January 2003 to March 2006 were reviewed for gestational age, birth weight, NAS score, dose of clonidine, duration of treatment, and additional medications required. RESULTS: Fourteen patients were identified. The mean gestational age was 30.1 weeks (range 24.4-40.7 weeks); three patients were full-term. Eleven had been on intravenous fentanyl for sedation; three were born to opioid-dependent mothers. All patients were treated with clonidine, administered in doses of 0.5-1.0 mcg/kg orally every 6 h. No patient received opioids. Mean duration of treatment was 6.8 days (range 4-15). Mean abstinence scores were 6.4 pretreatment (range 0-20) and 1.9 posttreatment (range 0-5). No patients suffered an adverse event (hypotension, bradycardia, excessive sedation, and oxygen desaturation) from clonidine administration, and no seizures were identified. CONCLUSIONS: Our data suggest that clonidine may be a reasonable alternative to more traditional agents used to prevent or treat NAS. We agree with the statement of the American Academy of Pediatrics Committee on Drugs that states that larger trials and pharmacologic data are needed before the routine use of clonidine can be recommended.

Parenteral ophthalmic tropicamide or cyclopentolate protects rats from lethal organophosphate poisoning.

We determine the efficacy of parenteral ophthalmic antimuscarinic agents (tropicamide ophthalmic 1% and cyclopentolate hydrochloride ophthalmic 1%) on survivability in a rat model of acute, lethal organophosphate pesticide (OP) poisoning. After obtaining an appropriate dose-response for study comparison, rodents were randomized to receive 1 of 4 intraperitoneal antidotes; (1) 0.3 mL normal saline, (2) atropine 10 mg/kg, (3) ophthalmic tropicamide 20 mg/kg, or (4) ophthalmic cyclopentolate 20 mg/kg. Five minutes after pretreatment, 15 mg/kg of dichlorvos was administered subcutaneously. Mortality rates and time to death were compared using Fisher exact test and the Kaplan-Meier method with log-rank test, respectively. If alive at 120 minutes, survival was assumed and the study was terminated. Survival in rats pretreated with atropine (10 mg/kg) was 90%. Survival in rats pretreated with tropicamide (20 mg/kg) and cyclopentolate (20 mg/kg) were 90% [P < 0.01; 95% confidence interval (CI) 0.71-1.09] and 90% (P < 0.01; 95% CI 0.71-1.09), respectively, compared with controls (10% survival; 95% CI 0.04-0.45). Time of death ranged between 6 and 13 minutes in nonsurvivors. Overall comparison of survival time revealed a statistically significant improvement in experimental groups compared with controls (P < 0.0001). Pretreatment with parenteral ophthalmic solutions (tropicamide or cyclopentolate) was equivalent to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.

Pretreating rats with parenteral ophthalmic antimuscarinic agents decreases mortality from lethal organophosphate poisoning.

BACKGROUND: In the event of a large scale organophosphate (OP) or nerve agent exposure that depletes a hospital's atropine stores, alternative antidotes should be considered. OBJECTIVES: To test the effects of parenteral administration of ophthalmic antimuscarinic agents on survivability in a rat model of acute, lethal OP poisoning. METHODS: After determining appropriate dosing for comparison, rodents were randomized to receive one of four intraperitoneal antidotes (n = 10 per group): 1) normal saline (0.3 mL), 2) atropine sulfate (10 mg/kg), 3) ophthalmic atropine sulfate (1%; 10 mg/kg), or 4) ophthalmic homatropine (5%; 20 mg/kg). Five minutes after pretreatment, dichlorvos (10 mg/kg) was administered subcutaneously. Mortality rates and time to death were compared by using Fisher's exact test and the Kaplan-Meier method with log rank test, respectively. If the animal was alive at 120 minutes, survival was assumed. RESULTS: Survival in rats pretreated with standard atropine was 100%. Survival in rats pretreated with ophthalmic homatropine and atropine sulfate were 100% (p < 0.001; 95% CI = 0.98 to 1.02) and 90% (p < 0.01; 95% CI = 0.71 to 1.09), respectively, compared with controls (20% survival; 95% CI = 0.04 to 0.45). Time of death ranged between 7 and 19 minutes. Comparison of survival times revealed a statistically significant improvement in experimental groups compared with controls (p < 0.0001). CONCLUSIONS: Parenteral pretreatment with ophthalmic preparations of homatropine or atropine sulfate was equal to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.

Intramuscular ophthalmic homatropine vs. atropine to prevent lethality in rates with dichlorvos poisoning.

INTRODUCTION: Most hospitals lack a sufficient supply of atropine to treat, simultaneously, patients poisoned with multiple organophosphorous compound (OC) or nerve agent. The presence of a ubiquitous alternate antidote would prove useful if mass poisoning occurred. Our objective was to evaluate the effect of ophthalmic homatropine (Isopto Homatropine 5%) on survivability in a rat model of significant, acute OC poisoning. METHODS: Sprague-Dawley rats were randomized to one of five pre-treatment groups (N = 10 per group). Prior to experimentation, animals were pre-treated with intramuscular (IM) injections of either atropine 5 mg/kg, atropine 10 mg/kg, homatropine 10 mg/kg, or homatropine 20 mg/kg. The control group received 0.3 mL normal saline IM. Five minutes later, 25 mg/kg of dichlorvos was subcutaneously administered. Mortality rates were compared using Fisher's Exact test. Kaplan-Meier survival curves with Logrank analysis was also performed. If alive at 120 minutes, survival was assumed, and the study was terminated. RESULTS: All rats pre-treated with normal saline, atropine 5 mg/kg, and homatropine 10 mg/kg died. Survival in the homatropine (20 mg/kg) and atropine (10 mg/kg) groups was 30% and 40% respectively. Times to death ranged between 4 and 12 minutes. Overall comparison of time to death revealed a statistically significant improvement for groups pre-treated with homatropine (20 mg/kg) and atropine (10 mg/kg). CONCLUSIONS: Pre-treatment with homatropine (20 mg/kg) was comparable with atropine (10 mg/kg) in preventing lethality in this rat model of acute OC poisoning.

Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey.

BACKGROUND: Important recent work has demonstrated that the use of induced hypothermia can improve survival and neurologic recovery after cardiac arrest. We wished to ascertain the extent to which physicians were using this treatment, and what opinions are held by clinicians regarding its use. METHODS: An internet-based survey of physicians was conducted, with physicians chosen at random from published directories of the Society for Academic Emergency Medicine, the American Thoracic Society, and the American Heart Association. Physicians were questioned regarding use of therapeutic hypothermia, methods employed, and/or reasons why they had not incorporated hypothermia into their care of cardiac arrest patients. RESULTS: Completed surveys were collected from 265 physicians, including those practicing emergency medicine (41%), critical care (13%), and cardiology (24%). Respondents were geographically well distributed and the majority (94%) were at post-training level. Most respondents (78%) practiced at either larger referral hospitals or academic medical centers. When asked if they had ever used hypothermia following cardiac arrest, 87% said they had not. Among reasons cited for non-use, 49% felt that there were not enough data, 32% mentioned lack of incorporation of hypothermia into advanced cardiovascular life support (ACLS) protocols, and 28% felt that cooling methods were technically too difficult or too slow. CONCLUSION: Despite compelling data supporting its use, hypothermia has yet to be broadly incorporated into physician practice. This highlights the need for improved awareness and education regarding this treatment option, as well as the need to consider hypothermia protocols for inclusion in future iterations of ACLS.