Sule Kalkan

Interrelation between the Poisoning Severity Score, carboxyhaemoglobin levels and in-hospital clinical course of carbon monoxide poisoning

The aim of the present study is to evaluate the relationship between the Poisoning Severity Score (PSS) and carboxyhaemoglobin (COHb) levels in patients with carbon monoxide poisoning (COP) using outcome as the measure. The study was designed as a retrospective chart review of patients with final diagnosis of COP. Correlation of PSS and COHb levels at presentation was evaluated with collected data. Majority of the cases were grade 1 (minor) PSS (134 cases, 73.6%) and 93.4% of these patients made a complete recovery. There were six deaths (mortality 3.3%) and six in‐hospital major complications (IHMCs) (3.3%) (please specify whether the complications were in the patients who died). There is moderate correlation between PSS and outcome (p < 0.001, r = 0.493). Grade 3 (severe) PSS was significantly different from other grades for outcome (six mortalities and three IHMCs). Patients classified as grade 3 and patients who died had a significantly higher mean age (p < 0.05, 41.8 ± 23.6 and p < 0.01, 60.1 ± 20.3, respectively). Mean COHb level of grade 3 (33.2 ± 13.9%) was significantly higher than that of other grades (p < 0.05). COHb levels according to outcome were not different (? within the patients in grade 3). Decreased level of consciousness, acidosis, tachycardia, high glucose and leucocyte levels showed significant relation with higher PSS, COHb level and adverse outcome. We conclude that the PSS is a reliable guide in COP. Value of the PSS in COP may be enhanced if additional factors and investigations are included.

Do Adenosine Receptors Play a Role in Amitriptyline‐Induced Cardiovascular Toxicity in Rats?

Objective: The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline‐induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication. Methods: Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40–45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor‐mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n = 8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8‐cyclopentyl‐1,3‐Dipropylxanthine, 20 µg/kg/min, n = 8) or a selective A2a antagonist CSC (8‐(3‐chlorostyryl) caffeine, 24 µg/kg/min, n = 8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n = 8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 µg/kg/min, n = 8) or CSC (24 µg/kg/min, n = 8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate. Results: In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 ± 2.8%, 75.6 ± 4.7% and 50.1 ± 14.7%, p < 0.01, p < 0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p < 0.05) and increased median survival time significantly (log‐rank test, p < 0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 ± 2.6%, 102.4 ± 2.6%, 81.8 ± 5.4, p < 0.01 at 30 min; 98.0 ± 2.9%, 93.5 ± 6.0%, 64.9 ± 4.7, p < 0.001, p < 0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p < 0.05) and increased median survival time significantly (log‐rank test, p < 0.0001). Conclusion: Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline‐induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline‐induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline‐induced cardiovascular toxicity.

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP.Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.

Evaluation of caustics and household detergents exposures in an emergency service.

Objective: The aim of this study was to analyse the caustic and household detergent exposure cases were admitted to the Department of Emergency Medicine at Dokuz Eylul University Hospital (EMDEU) between 1993 and 2008. Methods: Age, sex, reason of exposure, clinical signs, rate of endoscopy in oral exposures, treatment attempts, length of hospital stay and outcome were evaluated. A chi-square test was used to analyse statistical differences. Results: Caustic exposures accounted for 8.5% (1160 cases) and 4.1% (1988 cases) of all poisonings in children and adults, respectively. Female/male ratio of caustic exposure poisonings was 0.8. Most of the exposures were unintentional (158, 86.8%). Intentional exposures were common in cases between 19 and 29 years old (χ2 = 25.685, p < 0.001). The most common caustic substance was alkaline (106, 58.3%) followed by acidic (47, 25.8%) and other household detergents (28, 15.4%). Vomiting (35.7%), nausea (14.8%) and sore throat (13.1%) were the most common clinical signs. The patients who had endoscopy, the most frequent finding was first-degree damage (58.7%). A 48-year-old man died from intentional hydrochloric acid ingestion. Conclusion: Because of the large number of unintentional caustic exposures, parent education is very important to decrease the caustic exposures in children.

Effects of terlipressin in a rat model of severe uncontrolled hemorrhage via liver injury

BACKGROUND Animal experiments and clinical studies have shown that vasopressin infusion in cases of uncontrolled hemorrhagic shock is a promising treatment. However, there are only a few studies regarding the application of terlipressin in hemorrhagic cases. This study was designed to evaluate the effects of terlipressin vs controlled fluid resuscitation on hemodynamic variables and abdominal bleeding in a rat model of uncontrolled hemorrhage via liver injury. METHODS A total of 21 average weight 250 ± 30 g Wistar rats were used. A midline celiotomy was performed, and approximately 65% of the median and left lateral lobes were removed with sharp dissection. After creation of the liver injury, rats were randomized into 1 of 3 resuscitation groups, the control group, Lactated Ringers (LR) group, and terlipressin group, with 7 rats in each group. Blood samples were taken from rats for arterial blood gas analysis. At the end of the experiments, free intraperitoneal blood was collected on preweighed pieces of cotton, and the amount of free blood was determined by the difference in wet and dry weights. RESULTS In response to resuscitation, the terlipressin group demonstrated a significant elevation in mean arterial pressure (MAP). Blood loss was greater in the LR group compared with the control group (12.8 ± 1.9 mL vs 8.2 ± 0.7 mL, P < .05). At the end of the experiments, 5 rats in the control group, 5 in the LR group, and 2 in the terlipressin group died. The average survival rates were 28.6%, 28.6%, and 71.4%, respectively. CONCLUSIONS Compared with the control group, intravenous terlipressin bolus after liver injury contributed to an increase in MAP and survival rates without increasing abdominal bleeding.

Effects of adenosine receptor antagonists on amitriptyline-induced QRS prolongation in isolated rat hearts.

Objective. We investigated the effects of adenosine receptor antagonists on amitriptyline-induced cardiotoxicity in isolated rat hearts. Methods. The amitriptyline concentrations that prolonged the QRS duration more than 150% (10−4 M) and 50–75% (5.5 × 10−5 M) were accepted as the control groups for two experimental protocols, respectively. In the first protocol, amitriptyline (10−4 M) was infused following pretreatment with a selective adenosine A1 receptor antagonist, DPCPX (8-cyclopentyl-1,3-Dipropylxanthine,10−4 to 10−6 M) or a selective adenosine A2a receptor antagonist, CSC (8-3-chlorostyryl-caffeine,10−4 to 10−6 M). In the second protocol, amitriptyline (5.5 × 10−5 M) was infused following pretreatment with DPCPX (10−4 M) or CSC (10−5 M). Left ventricular developed pressure (LVDP), dp/dtmax, QRS duration and heart rate (HR) were measured. Results. In the first protocol, 10−4 M DPCPX pretreatment shortened QRS duration at 50 minutes when compared to the control group (p < 0.05). In the second protocol, pretreatment with 10−4 M DPCPX shortened the QRS duration at 40, 50, and 60 minutes after amitriptyline infusion when compared to the control group (p < 0.05, p < 0.01 and p < 0.05, respectively). Pretreatment with 10−5 M CSC prolonged QRS duration at 20, 30, and 60 minutes (p < 0.05). Amitriptyline infusion following pretreatment with DPCPX or CSC did not change LVDP, dp/dtmax, or HR when compared to control in both protocols (p > 0.05). Conclusion. While 10−4 M DPCPX shortened QRS prolongation, 10−5 M CSC prolonged QRS duration in the isolated rat hearts with prolonged QRS duration induced by 5.5 × 10−5M amitriptyline. An adenosine A1 receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.

Effect of glucagon on amitriptyline-induced cardiovascular toxicity in rats.

The aim of this study was to investigate the effect of glucagon on cardiovascular parameters in anesthetized rat model of tricyclic antidepressant overdose. Toxicity was induced by infusion of amitriptyline 0.94 mg/kg/min until a 40–45% of reduction in mean arterial pressure was observed. Amitriptyline infusion rats were then randomized into three groups. Control group of rats (group 1) received a bolus of 5% dextrose followed by the continuous infusion of dextrose, whereas treatment groups received 1 mg/kg (group 2) or 2 mg/kg (group 3) bolus doses of glucagon followed by continuous infusion (0.1 mg/kg/min) of glucagons for 60 min. Mean arterial pressure, heart rate, and electrocardiogram were recorded. Amitriptyline caused a significant decrease in mean arterial pressure and a prolongation in QRS, yet it did not change the heart rate. High-bolus dose of glucagon (2 mg/kg) followed by glucagon infusion significantly increased mean arterial pressure at 40, 50, and 60 min (P < 0.05) and shortened the prolonged QRS at 50 and 60 min (P < 0.05) when compared with control group. There was also a significant increase in heart rate. In conclusion, bolus doses followed by a continuous infusion of glucagon were found to be effective in reversing the hypotension and QRS prolongation in the rat model of amitriptyline toxicity. Further studies are needed to reveal the exact mechanism of the proposed effect.

The effects of captopril on serum digoxin levels in patients with severe congestive heart failure.

The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/-3.4 ng x h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.

Effects of Subchronic Parathion Exposure on Cyclosporine Pharmacokinetics in Rats

Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450) enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450- dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs that are metabolized in the liver. The CYP3A family is known to be responsible for the majority of cyclosporine metabolism. The aim of the present study was to assess the disposition kinetics of cyclosporine during subchronic parathion exposure. Male Wistar rats were administered either water or two different doses of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk. Subsequently, rats in each experimental group received a single oral dose of cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid artery over a period of 48 h. Pharmacokinetic analysis showed that parathion increased the blood cyclosporine concentration twofold as evidenced by AUC (area under the curve), half life (t ½) and peak plasma concentration (C max). This may be due to inhibition of cyclosporine metabolism, an interaction that may be of clinical relevance in immunosuppression therapy.

Turkish Coffeehouse “Kahvehane’’ is An Important Tobacco Smoke Exposure Area in Turkey

This study was undertaken to investigate the extent of environmental tobacco smoke (ETS) exposure in coffeehouses, as these are commonly frequented public places in Turkey. From 86 coffeehouses in the 3 districts, 59 coffeehouse workers and 35 hospital staff members (as a control group) were evaluated. Participants answered a questionnaire about demographics, working characteristics, smoking behavior, and ETS exposure during their daily life lives. The amount of nicotine in hair was determined by using gas chromatography/mass spectrometry (GC/MS). The mean hair nicotine level of the nonsmoker and smoker coffeehouse workers were 23.2 ± 12.3 µg/g and 62.5 ± 49.8 µg/g, respectively. Among the hospital staff, mean hair nicotine levels were 4.5 ± 6 µg/g in nonsmokers and 30.6 ± 14 µg/g in smokers. Working in coffeehouses has a marked effect on hair nicotine levels and potential adverse health effects. The project was funded by Dokuz Eylul University, Research Fund grant 0909 99 02 09, awarded to Prof. Arif Cimrin, MD. The authors thank Peyton Jacob III for the internal standard (nicotine-d4) and pharmacist Ayse Sezgin for technical support.