- Email: [email protected]
Endotracheal naloxone in rabbits: No adverse effects on blood gases and lung tissue
ment.
52 Endotracheal Naloxone in Rabbits: No Adverse Effects on Blood Gases and Lung Tissue SC Rector, RW Geiss, K Beamer, P Legg/Emergency Service, and Departments of Surgery and Pathology, West Virginia School of Medicine, Morgantown We compared endotracheal naloxone with normal saline solution to study the effects on arterial blood gases and lung tissue in 16 rabbits. The pulmonary effects of endotracheal naloxone have not been studied previously. Eight rabbits received naloxone through an endotracheal tube, and eight controls received normal saline. Blood gases were sampled for 30 minutes. Four subject rabbits and four controls were killed after two days; the remaining rabbits were killed after six weeks. Microscopic analysis of lung tissue was done by a pathologist blinded to the identity of the specimens. There was no significant difference in blood gas values between the naloxone and control groups. By microscopy, there was no observed pattern of variance in pulmonary pathology between the subject and control groups. This experiment revealed no adverse effects on rabbit blood gases and lung tissue after one dose of endotracheal naloxone as compared with saline. Further study is needed before endotracheal naloxone can be considered safe for human use.
53 Pharmacologic Interventions in Acute Cocaine Toxicity M Smith, D Garner, J Niemann/Departments of Emergency Medicine and Cardiology, Harbor-UCLA Medical Center, Torrance, California Cocaine toxicity is an increasing cause of mortality among emergency department patients. Several experimental models of cocaine toxicitY in which subjects were pretreated with pharmacologic agents have appeared in the literature; however, no one has designed a model in which the subjects had cocaine administered before pharmacologic intervention. We sought to develop this model. Rats were catheterized chronically in the jugular vein and carotid artery, had a rectal temperature probe placed, and had their intra-arterial pressures and waveforms recorded. The LD50 of IV cocaine was determined to be 14 mg/kg, which was confirmed in a control group of ten rats with a 50% mortality. After experimentally ensuring their nonlethality, labetal01 , diazepam, chlorpromazine, dantrolene, propranolol, and nitrendipine were administered immediately after the LD50 dose of cocaine. Mortality increased in the labetalol and propranolol groups (P < .05, chisquare with Yates correction factor) and was statistically unchanged with the other agents. No universal antidote for cocaine toxicity was detected. Therapy should be directed toward treatment of symptoms.
54 Agents That Protect Against Cocaine-Induced Death and Seizures in Animals RW Derlet, TE Albertson/Divisions of Emergency Medicine and Clinical Toxicology, University of California, Davis, School of Medicine, Sacramento A number of agents were studied to determine their effectiveness in protecting rats against seizure or death induced by cocaine. In this model, control rats were given 70 mg/kg cocaine intraperitoneal!y. Control animals developed seizures 94% of the time, and 82% died in mean times of 6.4 + 0.4 and 10.0 _+ 0.7 minutes, respectively. Animals were given test agents intraperitoneally 30 minutes prior to injection of cocaine. In this model, significant efficacy against both cocaine-induced seizure and death was afforded by pretreatment with diazepam, pentobarbital, and the GABA uptake blocker SKF 10033A (P < .01). Only 10% of animals receiving diazepam at the highest dose (2.0 mg/kg) tested died. Haloperidol and propranolol tended to minimally decrease the death rate, but this did not reach statistical significance (P > .05). Ethosuximide, phenytoin, valproic acid, and labetalol had no effect in reducing the death rate; the calcium channel blockers verapamil, nifedipine, and diltiazem enhanced toxicity. Agents that enhance the effect of the central neurotransmitter gamma-aminobutyric acid appear to have the greatest efficacy in protecting against the toxic effects of cocaine, while other classic anticonvulsants, catecholamine blockers, and calcium channel blockers failed to protect.
55 Life-Threatening Events After Theophylline Intoxication: A Prospective Analysis of 144 Cases M Shannon, FH Lovejoy/The Children's Hospital, Harvard Medical 166/446
School, The Massachusetts Poison Control System, Boston To further characterize the appearance of life-threatening events (LTEs) such as seizures and severe cardiac arrhythmias, following theophylline intoxication (serum theophylline > 30 gg/mL), we followed 144 cases of theophylline poisoning referred to our poison center over a two-and-one-half-year period. Fifty-two patients had acute theophylline intoxication; 64 had chronic theophylline intoxication; and 28 had acute-on-chronic theophylline intoxication. Mean age of patients was 32 years (range, 3 days to 84 years); mean peak theophylline level was 59.4 gg/mL (range, 30 to 211 gg/mL}. Associated features included a mean potassium level of 314 mEq/L (range, 2.2 to 5.8 mEq/L), mean glucose of 173 mg/dL (range, 92 to 377 mg/dL), and tremors in 45 (31%). Thirty-nine patients (27%) had a LTE (seizures, 13; arrhythmias, 27). Nine patients died. Distinct features were found when acute and chronic theophylline intoxication patients were separated.
Acute Chronic
Peak Theophylline Level LTE No LTE P
LTE
117.6 48.1
18.1 63.3
60.7 48.6
<.0001 NS
Age (years) . No Lte P 20.1 31.0
NS <.0001
A stepwise logistic regression equation confirmed these correlations with age, peak theophylline level, and LTEs, excluding potassium and drug coingestion as significant covariables. On the basis of these data, we conclude that peak theophylline level predicts LTEs in patients with acute but not chronic theophylline intoxication, age predicts LTEs in patients with chronic but not acute theophylline intoxication, hemodialysis-perfusion is indicated in patients with acute theophylline intoxication and theophylline levels > 100 gg/mL, and hemodialysis-perfusion is indicated for patients who have chronic theophylline intoxication and theophylline levels of more than 45 gg/mL with age more than 60 years.
56 Initial ECG Findings in 187 Cases of Cyclic Antidepressant Overdose FW Lavoie, GG Gansert, RE Weiss/Department of Emergency Medicine, School of Medicine, University of Louisville, Louisville, Kentucky ECG changes associated with cyclic antidepressant (TCA) overdose have been the subject of many reports in the medical literature. Heart rate, QRS duration, QT interval, and most recently, the terminal 40 ms QRS (T40) axis have been reported to be valuable indicators of TCA overdose. To evaluate the discriminant and predictive abilities of these and other ECG parameters in TCA overdose, we retrospectively reviewed the charts of all overdose patients admitted to intensive care units of our facility during a 30month period. Of 401 patients reviewed, 358 had initial emergency department toxicologic screening, ECGs, and records available for analysis, and were included in the study. The study population was divided into two groups based on the presence or absence of TCA on toxicologic screens. The TCA+ group comprised 52.2% and the TCA- group 47.8% of the study population. Mean age was 33 _+ 11 years. P wave axis, PR interval, initial 40 ms QRS axis, and total QRS axis were not statistically different. QRS duration, QTc, T40 axis, and heart rate were all found to be independently significantly different between the two groups by t test (P < .001). Using commonly quoted discriminating values (_> 100 ms for QRS duration, _> 100/min for heart rate, and 130 ° to 270 ° for T40 axis), we calculated the sensitivities, specificitiesl and positive and negative predictive values (Table). Each parameter could be used to correctly classify only 60% to 62% of cases, with all four in combination correctly classifying only 66%. We conclude, despite recent reports, that ECG parameters, although helpful if present, cannot be relied on to include or exclude the diagnosis of TCA overdose. Parameter Heart rate QRS duration T40 axis QTc
Sensitivity(%)
Specificity(%)
Ppv
NPV
Pearson's R
68 44 29
59 83 83
0.64 0.74 0.65
0.63 0.42 0.53
0.0895 0.3351 0.2315 0.2292
57 China White Epidemic: An Eastern United States Emergency Department Experience ML Martin, J Hecker, RF Clark, JH Frye, DV Jehie, EJ Lucid/ Medical College of Pennsylvania, Allegheny Campus, Department of Emergency Medicine and Emergency Medicine Residency Program, Allegheny General Hospital, Pittsburgh, Pennsylvania China white (3-methyl fentanyl) (3ME), an extremely potent synthetic analogue of fentanyl, was implicated in a series of
Annals of Emergency Medicine
18:4 April 1989
52 Endotracheal Naloxone in Rabbits: No Adverse Effects on Blood Gases and Lung Tissue SC Rector, RW Geiss, K Beamer, P Legg/Emergency Service, and Departments of Surgery and Pathology, West Virginia School of Medicine, Morgantown We compared endotracheal naloxone with normal saline solution to study the effects on arterial blood gases and lung tissue in 16 rabbits. The pulmonary effects of endotracheal naloxone have not been studied previously. Eight rabbits received naloxone through an endotracheal tube, and eight controls received normal saline. Blood gases were sampled for 30 minutes. Four subject rabbits and four controls were killed after two days; the remaining rabbits were killed after six weeks. Microscopic analysis of lung tissue was done by a pathologist blinded to the identity of the specimens. There was no significant difference in blood gas values between the naloxone and control groups. By microscopy, there was no observed pattern of variance in pulmonary pathology between the subject and control groups. This experiment revealed no adverse effects on rabbit blood gases and lung tissue after one dose of endotracheal naloxone as compared with saline. Further study is needed before endotracheal naloxone can be considered safe for human use.
53 Pharmacologic Interventions in Acute Cocaine Toxicity M Smith, D Garner, J Niemann/Departments of Emergency Medicine and Cardiology, Harbor-UCLA Medical Center, Torrance, California Cocaine toxicity is an increasing cause of mortality among emergency department patients. Several experimental models of cocaine toxicitY in which subjects were pretreated with pharmacologic agents have appeared in the literature; however, no one has designed a model in which the subjects had cocaine administered before pharmacologic intervention. We sought to develop this model. Rats were catheterized chronically in the jugular vein and carotid artery, had a rectal temperature probe placed, and had their intra-arterial pressures and waveforms recorded. The LD50 of IV cocaine was determined to be 14 mg/kg, which was confirmed in a control group of ten rats with a 50% mortality. After experimentally ensuring their nonlethality, labetal01 , diazepam, chlorpromazine, dantrolene, propranolol, and nitrendipine were administered immediately after the LD50 dose of cocaine. Mortality increased in the labetalol and propranolol groups (P < .05, chisquare with Yates correction factor) and was statistically unchanged with the other agents. No universal antidote for cocaine toxicity was detected. Therapy should be directed toward treatment of symptoms.
54 Agents That Protect Against Cocaine-Induced Death and Seizures in Animals RW Derlet, TE Albertson/Divisions of Emergency Medicine and Clinical Toxicology, University of California, Davis, School of Medicine, Sacramento A number of agents were studied to determine their effectiveness in protecting rats against seizure or death induced by cocaine. In this model, control rats were given 70 mg/kg cocaine intraperitoneal!y. Control animals developed seizures 94% of the time, and 82% died in mean times of 6.4 + 0.4 and 10.0 _+ 0.7 minutes, respectively. Animals were given test agents intraperitoneally 30 minutes prior to injection of cocaine. In this model, significant efficacy against both cocaine-induced seizure and death was afforded by pretreatment with diazepam, pentobarbital, and the GABA uptake blocker SKF 10033A (P < .01). Only 10% of animals receiving diazepam at the highest dose (2.0 mg/kg) tested died. Haloperidol and propranolol tended to minimally decrease the death rate, but this did not reach statistical significance (P > .05). Ethosuximide, phenytoin, valproic acid, and labetalol had no effect in reducing the death rate; the calcium channel blockers verapamil, nifedipine, and diltiazem enhanced toxicity. Agents that enhance the effect of the central neurotransmitter gamma-aminobutyric acid appear to have the greatest efficacy in protecting against the toxic effects of cocaine, while other classic anticonvulsants, catecholamine blockers, and calcium channel blockers failed to protect.
55 Life-Threatening Events After Theophylline Intoxication: A Prospective Analysis of 144 Cases M Shannon, FH Lovejoy/The Children's Hospital, Harvard Medical 166/446
School, The Massachusetts Poison Control System, Boston To further characterize the appearance of life-threatening events (LTEs) such as seizures and severe cardiac arrhythmias, following theophylline intoxication (serum theophylline > 30 gg/mL), we followed 144 cases of theophylline poisoning referred to our poison center over a two-and-one-half-year period. Fifty-two patients had acute theophylline intoxication; 64 had chronic theophylline intoxication; and 28 had acute-on-chronic theophylline intoxication. Mean age of patients was 32 years (range, 3 days to 84 years); mean peak theophylline level was 59.4 gg/mL (range, 30 to 211 gg/mL}. Associated features included a mean potassium level of 314 mEq/L (range, 2.2 to 5.8 mEq/L), mean glucose of 173 mg/dL (range, 92 to 377 mg/dL), and tremors in 45 (31%). Thirty-nine patients (27%) had a LTE (seizures, 13; arrhythmias, 27). Nine patients died. Distinct features were found when acute and chronic theophylline intoxication patients were separated.
Acute Chronic
Peak Theophylline Level LTE No LTE P
LTE
117.6 48.1
18.1 63.3
60.7 48.6
<.0001 NS
Age (years) . No Lte P 20.1 31.0
NS <.0001
A stepwise logistic regression equation confirmed these correlations with age, peak theophylline level, and LTEs, excluding potassium and drug coingestion as significant covariables. On the basis of these data, we conclude that peak theophylline level predicts LTEs in patients with acute but not chronic theophylline intoxication, age predicts LTEs in patients with chronic but not acute theophylline intoxication, hemodialysis-perfusion is indicated in patients with acute theophylline intoxication and theophylline levels > 100 gg/mL, and hemodialysis-perfusion is indicated for patients who have chronic theophylline intoxication and theophylline levels of more than 45 gg/mL with age more than 60 years.
56 Initial ECG Findings in 187 Cases of Cyclic Antidepressant Overdose FW Lavoie, GG Gansert, RE Weiss/Department of Emergency Medicine, School of Medicine, University of Louisville, Louisville, Kentucky ECG changes associated with cyclic antidepressant (TCA) overdose have been the subject of many reports in the medical literature. Heart rate, QRS duration, QT interval, and most recently, the terminal 40 ms QRS (T40) axis have been reported to be valuable indicators of TCA overdose. To evaluate the discriminant and predictive abilities of these and other ECG parameters in TCA overdose, we retrospectively reviewed the charts of all overdose patients admitted to intensive care units of our facility during a 30month period. Of 401 patients reviewed, 358 had initial emergency department toxicologic screening, ECGs, and records available for analysis, and were included in the study. The study population was divided into two groups based on the presence or absence of TCA on toxicologic screens. The TCA+ group comprised 52.2% and the TCA- group 47.8% of the study population. Mean age was 33 _+ 11 years. P wave axis, PR interval, initial 40 ms QRS axis, and total QRS axis were not statistically different. QRS duration, QTc, T40 axis, and heart rate were all found to be independently significantly different between the two groups by t test (P < .001). Using commonly quoted discriminating values (_> 100 ms for QRS duration, _> 100/min for heart rate, and 130 ° to 270 ° for T40 axis), we calculated the sensitivities, specificitiesl and positive and negative predictive values (Table). Each parameter could be used to correctly classify only 60% to 62% of cases, with all four in combination correctly classifying only 66%. We conclude, despite recent reports, that ECG parameters, although helpful if present, cannot be relied on to include or exclude the diagnosis of TCA overdose. Parameter Heart rate QRS duration T40 axis QTc
Sensitivity(%)
Specificity(%)
Ppv
NPV
Pearson's R
68 44 29
59 83 83
0.64 0.74 0.65
0.63 0.42 0.53
0.0895 0.3351 0.2315 0.2292
57 China White Epidemic: An Eastern United States Emergency Department Experience ML Martin, J Hecker, RF Clark, JH Frye, DV Jehie, EJ Lucid/ Medical College of Pennsylvania, Allegheny Campus, Department of Emergency Medicine and Emergency Medicine Residency Program, Allegheny General Hospital, Pittsburgh, Pennsylvania China white (3-methyl fentanyl) (3ME), an extremely potent synthetic analogue of fentanyl, was implicated in a series of
Annals of Emergency Medicine
18:4 April 1989