Atropine Group Research Articles

Is atropine needed with ketamine sedation? A prospective, randomised, double blind study

Objective: To compare atropine with placebo as an adjunct to ketamine sedation in children undergoing minor painful procedures. Outcome measures included hypersalivation, side effect profile, parental/patient satisfaction, and procedural success...

Prevention of Myopia Progression with 0.05% Atropine Solution

The aim of this study was to evaluate the efficacy of 0.05% atropine solution for controlling myopia progression in school-aged children. This retrospective, case-control study enrolled myopic school-aged children who had presented at Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan) from 2001 to 2004. A group of 57 children (30 boys, 27 girls; 6-12 years of age) with regular follow-up was divided into a subgroup of 21 children (12 boys, 9 girls) who received atropine eyedrops (0.05%) every evening, and a subgroup of 36 children (18 boys, 18 girls), who remained untreated, served as controls. The changes in refractive status of 114 eyes in 57 children were collected and compared for patients treated with 0.05% atropine eyedrop and those without medical control. The initial spherical equivalent of refractive status range was between -0.5 and -5.5 D. Mean myopia progression for the group of patients treated with 0.05% atropine eyedrop (n = 21) was -0.28 +/- 0.26 D/year, significantly lower than that of the control group of -0.75 +/- 0.35 D/year (36 patients; P < 0.001). The 0.05% atropine group had a significant lower ratio of uncontrolled myopia, that progressed greater than -0.50 D in 1 year, relative to the controls (16.7% versus 77.8%; P < 0.001). The results of this study demonstrate that, with regular instillation, topical 0.05% atropine is an effective agent for controlling myopia progression in a majority of school-aged children for at least a period of 1 year.

Influence of Atropine on the Dose Requirements of Propofol in Humans

The purpose of this study was to evaluate the effect of atropine on the dose requirement of propofol for induction of anesthesia and propofol concentrations during continuous infusion. Study 1: Forty patients were randomly allocated to the control or atropine groups. Induction of anesthesia commenced 3 min following the administration of 0.9% saline or atropine (0.01 mg kg(-1)), using a Diprifuser set to achieve propofol concentration of 6.0 microg mL(-1). The primary end point was the propofol dose per kg at the moment of loss of response to a command. Study 2: Fifteen patients undergoing elective surgery were enrolled. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 2.0 microg mL(-1) after intubation. Before and after administration of atropine (0.01 mg kg(-1)), cardiac output (CO) was measured using indocyanine green as an indicator and blood propofol concentration was determined using high-performance liquid chromatography. Study 1: The propofol dose for each group was 2.22+/-0.21 mg kg(-1) for control group and 2.45+/-0.28 mg kg(-1) for atropine, respectively (p=0.014). Study 2: After the administration of atropine, CO was significantly increased from 4.28+/-0.83 to 5.76+/-1.55 l min(-1) (p<0.0001). Propofol concentration was significantly decreased from 2.12+/-0.28 to 1.69+/-0.27 microg mL(-1) (p<0.0001). Following the administration of atropine, the propofol requirements for the induction of anesthesia were increased and propofol concentrations were decreased during continuous infusion by the administration of atropine.

The Effect of Amblyopia Therapy on Ocular Alignment

We sought to describe the change in ocular alignment at 2 years after treatment of amblyopia in children younger than 7 years of age at enrollment. A randomized clinical trial of patching versus atropine for 6 months followed by standard clinical care for 18 months was conducted in 357 children with anisometropic, strabismic, or combined amblyopia (20/40-20/100) whose ages ranged from 3 to younger than 7 years at enrollment. Ocular alignment was evaluated at enrollment and after 2 years of follow-up. At enrollment when tested at distance fixation, 161 (45%) children were orthotropic, 91 (25%) had a microtropia (1-8 Delta), and 105 (29%) had a heterotropia >8 Delta. Of the 161 patients with no strabismus, similar proportions of patients initially assigned to the patching and atropine groups developed new strabismus by 2 years (18% vs. 16%, P = 0.84). Of these cases of new strabismus, only 2 patients in the patching group and 3 patients in the atropine group developed a deviation that was greater than 8 Delta. Microtropia at enrollment progressed to a deviation greater than 8 Delta with similar frequency in both treatment groups (13% vs. 15%, P = 1.00). Of the 105 patients with strabismus greater than 8 Delta at enrollment, 13% of those in the patching group and 16% of those in the atropine group improved to orthotropia without strabismus surgery. Strabismus surgery was performed in 32 patients during the 2-year study period. Patients who had amblyopia treatment with patching or atropine for 6 months followed by standard clinical care were found to have similar rates of deterioration and improvement of ocular alignment. When parents begin amblyopia treatment for children without strabismus, they should be warned of the possibility of development of strabismus, although it is most often a small angle deviation. Strabismus resolved after amblyopia therapy in some cases.

Carotid angioplasty and stent-induced bradycardia and hypotension: Impact of prophylactic atropine administration and prior carotid endarterectomy

We compared the physiologic effect of selective atropine administration for bradycardia with routine prophylactic administration, before balloon inflation, during carotid angioplasty and stenting (CAS). We also compared the incidence of procedural bradycardia and hypotension for CAS in patients with primary stenosis vs those with prior ipsilateral carotid endarterectomy (CEA). A total of 86 patients were treated with CAS at 3 institutions. Complete periprocedural information was available for 75 of these patients. The median degree of stenosis was 90% (range, 60%-99%). Indications for CAS were severe comorbidities (n = 49), prior CEA (n = 21), and prior neck radiation (n = 5). Twenty patients with primary lesions were treated selectively with atropine only if symptomatic bradycardia occurred (nonprophylactic group). Thirty-four patients with primary lesions received routine prophylactic atropine administration before balloon inflation or stent deployment (prophylactic group). The 21 patients with prior CEA received selective atropine treatment only if symptomatic bradycardia occurred (prior CEA group) and were analyzed separately. Mean age and cardiac comorbidities did not vary significantly either between the prophylactic and nonprophylactic atropine groups or between the primary and prior CEA patient groups. Outcome measures included bradycardia (decrease in heart rate >50% or absolute heart rate <40 bpm), hypotension (systolic blood pressure <90 mm Hg or mean blood pressure <50 mm Hg), requirement for vasopressors, and cardiac morbidity (myocardial infarction or congestive heart failure). The overall incidence of hypotension and bradycardia in patients treated with CAS was 25 (33%) of 75. A decreased incidence of intraoperative bradycardia (9% vs 50%; P < .001) and perioperative cardiac morbidity (0% vs 15%; P < .05) was observed in patients with primary stenosis who received prophylactic atropine as compared with patients who did not receive prophylactic atropine. CAS after prior CEA was associated with a significantly lower incidence of perioperative bradycardia (10% vs 33%; P < .05), hypotension (5% vs 32%; P < .05), and vasopressor requirement (5% vs 30%; P < .05), with a trend toward a lower incidence of cardiac morbidity (0% vs 6%; not significant) as compared with patients treated with CAS for primary carotid lesions. There were no significant predictive demographic factors for bradycardia and hypotension after CAS. The administration of prophylactic atropine before balloon inflation during CAS decreases the incidence of intraoperative bradycardia and cardiac morbidity in primary CAS patients. Periprocedural bradycardia, hypotension, and the need for vasopressors occur more frequently with primary CAS than with redo CAS procedures. On the basis of our data, we recommend that prophylactic atropine administration be considered in patients with primary carotid lesions undergoing CAS.

The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning

Organophosphate poisoning causes disturbances in cardiac conduction and potentially fatal severe cardiac rhythm abnormalities. This study investigated the cardiac effects of atropine and pralidoxime in the treatment of organophosphate poisoning in rats. Three groups of 10 adult male Wistar rats were anesthetized with an intraperitoneal injection of ketamine 100 mg/kg and xylazine 10 mg/kg and connected to a computerized electrocardiographic monitor. Each rat was then injected intraperitoneally with the pesticide dichlorvos 70 mg/kg. Sixty seconds after the injection, 10 rats were injected with saline, 10 with pralidoxime mesylate 20 mg/kg, and 10 with atropine 10 mg/kg. During the computerized electrocardiographic monitoring, each rat's heart rate and QT(c) intervals were recorded and analyzed as the injections were administered. The heart rates in all 3 groups did not differ before the dichlorvos was administered, nor at 60 seconds afterward, but in the atropine group, the time elapsed before the first decline in heart rate was significantly longer than that in the control group (P<.05). In addition, the interval before death was significantly longer in the atropine group than in either the control group or the pralidoxime group (P<.05 for both). The QT(c) was almost identical in each of the groups. Atropine has beneficial effects on the heart rate, prolongs the time before the heart rate declines, and delays death but has no effect on the QT(c) interval. Further research about the toxic effects of organophosphate compounds on myocardial cells is warranted.

Two-Year Follow-up of a 6-Month Randomized Trial of Atropine vs Patching for Treatment of Moderate Amblyopia in Children

To compare patching and atropine sulfate as treatments for moderate amblyopia in children 18 months after completion of a 6-month randomized trial. In a randomized, multicenter (47 sites) clinical trial, 419 children younger than 7 years with amblyopia (20/40 to 20/100 in the affected eye) were assigned to receive either patching or atropine eye drops for 6 months. Between 6 months and 2 years, treatment was at the discretion of the investigator. Main Outcome Measure Visual acuity in the amblyopic eye and sound eye after 2 years. At 2 years, visual acuity in the amblyopic eye improved from baseline a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. The difference in visual acuity between treatment groups was small: 0.01 logMAR (95% confidence interval, -0.02 to 0.04). In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20. Atropine or patching for 6 months followed by best clinical care until 2 years produced similar improvement of moderate amblyopia in children between 3 and 7 years of age at enrollment. However, on average the amblyopic eye acuity was still approximately 2 lines worse than the sound eye.

Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study

Remifentanil is known to cause bradycardia and hypotension. We aimed to characterize the haemodynamic profile of remifentanil during sevoflurane anaesthesia in children with or without atropine. Forty children who required elective surgery received inhalational induction of anaesthesia using 8% sevoflurane. They were allocated randomly to receive either atropine, 20 microg kg(-1) (atropine group) or Ringer's lactate (control group) after 10 min of steady-state 1 MAC sevoflurane anaesthesia (baseline). Three minutes later (T0), all children received remifentanil 1 microg kg(-1) injected over a 60 s period, followed by an infusion of 0.25 microg kg(-1) min(-1) for 10 min then 0.5 microg kg(-1) min(-1) for 10 min. Haemodynamic variables and echocardiographic data were determined at baseline, T0, T5, T10, T15 and T20 min. Remifentanil caused a significant decrease in heart rate compared with the T0 value, which was greater at T20 than T10 in the two groups: however, the values at T10 and T20 were not significantly different from baseline in the atropine group. In comparison with T0, there was a significant fall in blood pressure in the two groups. Remifentanil caused a significant decrease in the cardiac index with or without atropine. Remifentanil did not cause variation in stroke volume (SV). In both groups, a significant increase in systemic vascular resistance occurred after administration of remifentanil. Contractility decreased significantly in the two groups, but this decrease remained moderate (between -2 and +2 sd). Remifentanil produced a fall in blood pressure and cardiac index, mainly as a result of a fall in heart rate. Although atropine was able to reduce the fall in heart rate, it did not completely prevent the reduction in cardiac index.

Pediatric rapid sequence intubation: incidence of reflex bradycardia and effects of pretreatment with atropine.

The American College of Emergency Physicians (ACEP) recommends atropine as adjunctive therapy to prevent reflex bradycardia prior to laryngoscopy/tracheal intubation (L/TI) in pediatric patients. To describe the incidence of reflex bradycardia and its relationship to the administration of atropine during L/TI in a Pediatric Emergency Department. A retrospective cohort study was designed through review of records of all patients who received L/TI in the ED at an urban children's hospital from January 1997 to March 2001. Patients meeting inclusion criteria were placed into cohorts defined by whether they had received atropine prior to L/TI or not. One hundred sixty-three patients received L/TI during the study period. One hundred forty-three patients met inclusion criteria. Sixty-eight patients received atropine (atropine group) prior to L/TI. Seventy-two percent of atropine group patients met ACEP criteria for atropine pretreatment. Seventy-five patients did not receive atropine pretreatment (no-atropine group). Forty-three percent of no-atropine group patients met ACEP criteria for pretreatment with atropine. The atropine group was younger [mean 22.5 vs. 36.4 months, P = 0.003, 95% CI (-28.5, 0.70)], averaged the same number of intubation attempts [1.6 vs. 1.5, P = 0.941, 95% CI 0.1 (-0.3,0.4)], and had normal or elevated HR for age prior to L/TI (mean 159 bpm). Hypoxia occurred more often in the atropine group [28% vs. 16%, P = 0.046, 95% CI for difference (0.3, 27.1)]. Bradycardia was noted in 6 patients during L/TI; 3 in the atropine group and 3 in the no-atropine group. Atropine is not routinely administered prior to L/TI in this pediatric ED. Pretreatment with atropine did not prevent bradycardia in all cases. These data suggest that use of atropine prior to L/TI may not be required for all pediatric patients. Some patients will experience bradycardia regardless of atropine pretreatment.

Evidence that muscarinic receptors are involved in nicotine-facilitated spatial memory

A delayed nonmatching-to-position task (DNMPT) in a water maze (nine trials per day, 10 days) was used to investigate the role of muscarinic acetylcholinergic receptor (mAChR) in nicotine-facilitated spatial memory in Wistar rats. The index of spatial memory was determined by the number of correct choices made in choice swim (CS) and the time taken to complete the swim in the correct CS. Diazepam (6 mg kg −1 ip, daily) significantly impaired choice accuracy and increased the swim time for correct CS. In contrast, when nicotine (2 mg kg −1 sc, twice daily) and diazepam were administered simultaneously in the last three sessions of training, the choice accuracies of CS were similar to controls and significantly higher than in the diazepam group. However, the swim times for correct CS were longer in the nicotine+diazepam group than in controls. Atropine (30 mg kg −1 ip, daily) significantly decreased the choice accuracies of CS. The choice accuracies of CS swim times for correct CS in the atropine group did not differ significantly from those in the nicotine+atropine group, in which nicotine (2 mg kg −1 sc, twice daily) and atropine were given simultaneously. These results show that nicotine improves memory performance when the functions of mAChRs are normal; when the mAChRs are blocked, nicotine does not enhance spatial memory. Therefore, mAChRs are involved in the spatial memory-enhancing effect of nicotine.

Core Temperature Changes according to Premedication

Background: It is well known that body core temperature reduces during general anesthesia. Midazolam premedication for relieving anxiety might also reduce body core temperature by inhibiting tonic thermoregulatory vasoconstriction in elderly patients. Therefore, an effort to maintain temperature must be started before anesthesia. This study was designed to evaluate the effect on body core temperature of midazolam, atropine and glycopyrrolate, which are commonly used for premedication. Methods: Six hundred and eleven patients of ASA physical status 1 or 2, aged 18 to 65, were involved in this study. They were randomly assigned to premedication with: 1) saline control (n = 92); 2) midazolam 0.04 mg/kg (n = 96); 3) midazolam 0.04 mg/kg with glycopyrrolate 0.004 mg/kg (n = 117); 4) midazolam 0.04 mg/kg with atropine 0.01 mg/kg (n = 93); 5) glycopyrrolate 0.004 mg/kg (n = 116); and 6) atropine 0.01 mg/kg (n = 97). All premedication was given intramuscularly about 30 min before operation. Temperatures were measured at the tympanic membrane at the time of premedication and 30 min after premedication. Results: Temperatures increased slightly after injection in the control (0.14 ; mean SD) and this increase was less in the midazolam group (0.07 . The changes of temperature in the midazolam with glycopyrrolate (0.16 . midazolam with atropine (0.19 . ), and in the glycopyrrolate group were no different from that of the control group. However, there was a statistically significant increase in temperature after injection in the atropine group (0.26 ) versus the control group. Compared with the midazolam group, a statistically significant increase in temperature was observed in the midazolam with atropine, the glycopyrrolate, and in the atropine group. Conclusions: From these results, low dose midazolam (0.04 mg/kg), midazolam with glycopyrrolate, and midazolam with atropine for premedication have little affect on temperature. Midazolam with glycopyrrolate premedication is recommended for preserving body core temperature.

The Effect of Intravenous Midazolam or Atropine on Spinal Anesthesia-Induced Hypothermia in Geriatric Patients

Background: Perioperative hypothermia causes several complications, and in particular, is more hazardous in elderly patients. Hypothermia during regional anesthesia is often ignored. We investigated the effect of IV midazolam or atropine premedication on core hypothermia in geriatric patients undergoing transurethral predures via spinal anesthesia. Methods: Forty-five elderly (65-92 years old), ASA I or II patients about to undergo transurethral predures, such as prostate or bladder tumor removal were enrolled into this study. In all cases, standard spinal anesthesia was administered. The control group received no premedication, the midazolam group 0.02 mg/kg of midazolam, and the atropine group 5/kg of atropine, respectively just before spinal anesthesia. Core temperature was measured at the right tympanic membrane before anesthesia, at 10 and 30 min later, at the end of anesthesia, and 30 min after recovery from anesthesia. Results: Reduction of core temperature from the basal value, after 10 and 30 min of anesthesia, at the end of anesthesia, at 30 min after anesthesia during post-operative care unit in the control group were 0.31, 0.61, 0.5, and 0.42, respectively; 0.41, 0.61, 0.9, 0.65 in the midazolam group; and 0.15, 0.29, 0.37, 0.47 in the atropine group. When compared with no premedication, midazolam administration was assiated with a significantly lower core temperature at the end of anesthesia. Atropine administration was assiated with a significantly higher core temperature than the midazolam group after 10 and 30 min of anesthesia, and at the end of anesthesia, and the untreated control group after 10 and 30 min of anesthesia. Conclusions: IV premedicant midazolam decreased core temperature; however, atropine administration significantly reduced the magnitude of hypothermia assiated with spinal anesthesia in geriatric patients.

Changes in Swallowing-Related Tachycardia and Respiratory Arrhythmia Induced by Modulation of Tonic Parasympathetic Influences

In 19 tested persons in the resting lying position, we examined changes in the mean duration of R-R intervals \((\overline {R - R} )\) and in parasympathetic chronotropic cardiac reactions (respiratory arrhythmia,RA, and swallowing-related tachycardia, ST) induced by intensified tonic parasympathetic influences after peroral administration of antagonists of muscarinic (M) receptors in small doses. Administration of 0.02 g of an extract of Belladonna, which contains alkaloids of the atropine group, led to a significant \(\overline {R - R} \) increase (P < 0.001). In this case, the RA at the natural frequency of breathing (P < 0.05) and ST (P < 0.001) simultaneously increased. Close correlation was observed both between initial values of the ST and \(\overline {R - R} \) in various tested persons (r = 0.87) and between changes in these values, which were induced by the action of small amounts of M antagonists (r = 84). In various persons, the RA during deep slowed breathing (6 min-1, RA6) demonstrated ambiguous modifications. In the structure of RA6, we identified two components: an inspiratory tachycardic (TC) and an expiratory bradycardic (BC). With intensification of the parasympathetic influences, the TC began to prevail; its increase was strongly related to a rise in the \(\overline {R - R} \) (r = 0.84). In contrast, correlation between changes in the BC and an increase in the \(\overline {R - R} \) was completely absent (r = 0.001). Therefore, small amounts of M antagonists intensify both the tonic component of parasympathetic control (increasing the \(\overline {R - R} \)) and its dynamic indices, the magnitudes of the ST and RA. Tachycardia during swallowing and the inspiratory TC under conditions of deep slowed breathing are closely related to changes in the parasympathetic influences. The magnitude of the RA is the index, which reflects the tonic component of chtonotropic control under conditions of both slowed and natural breathing less adequately than the ST.

A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors

Objective To assess whether the relative treatment effect of patching compared with atropine for moderate amblyopia varies according to patient age, cause of amblyopia or depth of amblyopia, and initial number of patching hours prescribed. Design Multicenter, randomized clinical trial. Participants Four hundred nineteen children younger than 7 years of age with amblyopia in the range of 20/40 to 20/100. Methods Patients were assigned randomly to receive treatment with either patching or atropine and followed up for 6 months. Primary outcome measure Single-surrounded HOTV optotype visual acuity in the amblyopic eye after 6 months. Results Improvement in the amblyopic eye visual acuity was slightly greater in the patching group compared with the atropine group in all subgroups based on patient characteristics. The relative treatment effect did not vary with age ( P = 0.84), cause of amblyopia ( P = 0.68), or baseline amblyopic eye acuity ( P = 0.59). Patients with acuity of 20/80 to 20/100 who were prescribed 10 or more hours a day of patching showed a more rapid improvement in acuity than did patients prescribed a lesser amount of patching ( P = 0.01) or than did patients in the atropine group ( P < 0.001), but by 6 months, the differences were not significant ( P = 0.47 and 0.15, respectively). Conclusions A beneficial effect of both patching and atropine is present throughout the age range of 3 to younger than 7 years old and the acuity range of 20/40 to 20/100. Patients with acuity of 20/80 to 20/100 improve faster when a greater number of hours of patching is prescribed, but by 6 months, the amount of improvement is not related to the number of hours of patching initially prescribed.

Ontogeny of cholinergic regulation of fetal upper gastrointestinal motility

Objective: In the fetal rabbit immediately prior to birth (day 30; 0.97 gestation), intragastric atropine suppresses upper gastrointestinal (GI) motility, indicating that cholinergic receptors are expressed and functional at birth. To explore the developmental timing of upper GI cholinergic receptor function, we assessed the effect of intragastric atropine administration in rabbit fetuses during the last 10% of gestation. Methods: Pregnant rabbits were studied at day 27, day 28 and day 29 of their normal 31-day gestation. In each litter, two fetuses were selected as study fetuses and two as control fetuses. Under ultrasound guidance, fluorescein and either atropine (0.04 μg/g fetal body weight) or normal saline were injected into the fetal stomach. Two hours after injection, fetuses were delivered and the small intestine was harvested. The per cent motility was calculated as the fluorescein travel distance, which was measured by ultraviolet light optical density, divided by the total small intestinal length. Results: Fetal body weight, small intestinal length and per cent motility increased from day 27 to day 29 (p < 0.01). There were no differences in fetal body weight and small intestinal length between atropine and control groups. Atropine significantly decreased per cent motility (versus control values) in fetuses at day 29 and day 28 (56.1 ± 13.5 vs. 66.1 ± 11.7% and 59.7 ± 15.6 vs. 68.3 ± 11.7%, respectively; p < 0.05), but not at day 27 (52.4 ± 12.9 vs. 52.8 ± 11.2%). Conclusions: These results indicate that upper GI functional cholinergic receptors develop between 0.87 and 0.90 of rabbit gestation. Extrapolation to human development suggests that reduced GI motility in preterm human infants results, in part, from immature GI cholinergic receptors.

Oral treatment of organophosphate poisoning in mice.

Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi-square analysis was used to compare results in the different groups. Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.

Oral Treatment of Organophosphate Poisoning in Mice

Abstract Objective: Organophosphates are used as pesticides, herbicides, and chemical warfare agents. Treatment of organophosphate poisoning is with intravenous atropine and pralidoxime in addition to supportive care. This study determined the efficacy of oral agents in preventing death from organophosphate poisoning. Methods: The organophosphate paraoxon (8 mg/kg) was used in a murine model with lethality at four and 24 hours as an end point. For oral treatment, 15 male Balbc mice were given either atropine sulfate (4 mg/kg), or a combination of atropine sulfate (4 mg/kg) with pralidoxime (100 mg/kg), by oral gavage. A control group of 22 mice received water by oral gavage. Chi‐square analysis was used to compare results in the different groups. Results: Of the control group, six of 22 survived to four hours after paraoxon exposure. Of the exposed animals treated with oral atropine, eight of 15 survived to four hours. Of the exposed animals treated with a combination of atropine and pralidoxime, 13 of 15 survived to four hours. All animals surviving to four hours survived to 24 hours. The increased survival of animals in the atropine group relative to the control group was not significant (p = 0.09). Survival was significant in the group treated with atropine and pralidoxime relative to atropine alone (p = 0.02) and to the control group (p = 0.0002). All treated mice surviving at four hours were alive at 24 hours. Conclusions: Both oral atropine and a combination of oral atropine and pralidoxime improved survival, and combination therapy achieved statistical significance. Generalization of this result to other organophosphate pesticides, other doses of paraoxon, and other species cannot be made without further investigations.

Effects of Preinduction Atropine on the Hemodynamic Response to Induction with Fentanyl and Vecuronium for Coronary Artery Bypass Grafting

Background: Induction of anesthesia with a high dose of fentanyl and vecuronium decreases the heart rate and blood pressure. This study was designed to evaluate the effect of preinduction atropine on these hemodynamic changes in patients undergoing coronary artery bypass graft surgery (CABG). Methods: Forty-one patients who underwent CABG were randomly divided into two groups. After insertion of a radial artery cannula and a Swan-Ganz catheter, normal saline 1 ml (control group, n = 20) or atropine 0.5 mg (atropine group, n = 21) was injected intravenously 1 min before the induction of anesthesia. Anesthesia was induced with a first dose of fentanyl (5-8/kg) and vecuronium (0.12 mg/kg) and a second dose of fentanyl (5-10/kg). The patient was then intubated. Hemodynamic variables were measured before the induction of anesthesia, 1 min after the administration of each drug during the induction of anesthesia and 5, 10, and 30 min after the intubation. Results: There was no significant differences between the two groups in terms of demographic data except that the number of patients with diabetes mellitus was greater in the control group than in the atropine group. The number of patients treated for hypotension or bradycardia during the induction of anesthesia was greater in the control group than in the atropine group, but this was not statistically significant. Heart rates significantly decreased in the control group but were maintained in the atropine group without any significant tachycardia. Blood pressure significantly decreased in both groups. Conclusions: Intravenous injection of atropine before anesthetic induction in patients undergoing CABG attenuates the decrease in heart rate resulting from anesthetic induction with high dose fentanyl and vecuronium. However, it didn't prevent the decrease in blood pressure nor did it reduce the incidence of treatment for hypotension.

Ontogeny of cholinergic regulation of fetal upper gastrointestinal motility

Objective: In the fetal rabbit immediately prior to birth (day 30; 0.97 gestation), intragastric atropine suppresses upper gastrointestinal (GI) motility, indicating that cholinergic receptors areexpressed and functional at birth. To explore the developmental timing of upper GI cholinergic receptor function, we assessed the effect of intragastric atropine administration in rabbit fetuses duringthe last 10% of gestation.Methods: Pregnant rabbits were studied at day 27, day 28 and day 29 of their normal 31-day gestation. In each litter, two fetuses were selected as study fetuses andtwo as control fetuses. Under ultrasound guidance, fluorescein and either atropine (0.04 μg/g fetal body weight) or normal saline were injected into the fetal stomach. Two hours after injection, fetuseswere delivered and the small intestine was harvested. The per cent motility was calculated as the fluorescein travel distance, which was measured by ultraviolet light optical density, divided by the totalsmall intestinal length.Results: Fetal body weight, small intestinal length and per cent motility increased from day 27 to day 29 (p < 0.01). There were no differences in fetal bodyweight and small intestinal length between atropine and control groups. Atropine significantly decreased per cent motility (versus control values) in fetuses at day 29 and day 28 (56.1 ± 13.5 vs.66.1 ± 11.7% and 59.7 ± 15.6 vs. 68.3 ± 11.7%, respectively; p < 0.05), but not at day 27 (52.4 ± 12.9 vs. 52.8 ± 11.2%).Conclusions: These resultsindicate that upper GI functional cholinergic receptors develop between 0.87 and 0.90 of rabbit gestation. Extrapolation to human development suggests that reduced GI motility in preterm human infants results,in part, from immature GI cholinergic receptors.

Diphenhydramine as a Protective Agent in a Rat Model of Acute, Lethal Organophosphate Poisoning

Objective: To evaluate the effects of diphenhydramine chloride (DPH) on mortality in a rat model of acute, severe organophosphate poisoning (OP).Methods: Wistar rats (n = 40) were randomized to pretreatment with either normal saline (controls), 5 mg/kg atropine, 3 mg/kg DPH, 15 mg/kg DPH, or 30 mg/kg DPH given as a single intramuscular injection 5 minutes prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). The primary endpoint was 10‐minute survival. Survival at 24 hours was a secondary endpoint. Comparison of survival rates between groups was carried out by ANOVA and the Student‐Newman‐Keuls test. Results: Dichlorvos exposure resulted in profound fasciculations within 2 minutes of injection in all cohorts. In controls, fasciculations were followed by respiratory arrest within 10 minutes (0% survival). The rats receiving atropine pre‐treatment exhibited similar fasciculations (nicotinic effects) without subsequent respiratory arrest, resulting in a significant improvement in survival (88%, p &lt; 0.001). The DPH‐treated rats exhibited a significant dose‐dependent reduction in mortality, with the 3 mg/kg, 15 mg/kg, and 30 mg/kg groups demonstrating 0%, 25%, and 100% survival, respectively. There was no additional mortality between 10 minutes and 24 hours in any group. There was no significant difference in survival between the high‐dose DPH and the atropine groups. Conclusions: Diphenhydramine chloride significantly reduced mortality in rats with acute, severe dichlorvos exposure.