Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: Evidence for differential roles of muscarinic and nicotinic stimulation

Background. Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at these different phases may have important clinical implications. Objective. To compare the electrophysiological findings in patients with early and late respiratory failure following acute OP poisoning. Methods. A prospective observational case series of consenting symptomatic patients with acute OP poisoning were assessed with daily physical examinations and repetitive nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and development of intermediate syndrome (IMS) were noted. Early respiratory failure was defined as occurring within 24 hours of ingestion. Results. Seventy-eight patients were recruited for the clinical and electrophysiological study and of those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed respiratory failure within 24 hours of ingestion with overt muscarinic signs. They had no electrophysiological abnormalities at median and ulnar nerves before intubation. Three of them later developed “forme fruste” IMS. Five other patients developed late respiratory failure after 24 hours of ingestion, and all of them showed progressive RNS changes indicating severe IMS prior to intubation. Conclusion. The normal RNS in all patients developing early respiratory failure suggests that it is due to a central nervous system (CNS) and muscarinic effect. This emphasizes the need for early rapid atropinisation as a priority, combating the nicotinic effects being less urgent. This is in contrast with the late respiratory failure, which has been shown to be associated with neuromuscular dysfunction. Further studies are needed to quantify CNS and muscarinic dysfunction to assist in the development of better treatments for the severe and early OP poisoning.     

Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization

Objectives

Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses.

Design and Patients

Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study.

Results

Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant (P < .0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure.

Conclusions

Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis < metabolic acidosis < respiratory acidosis < mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.     

Diagnosis in an acute organophosphate poisoning: report of three interesting cases and review of the literature.

Organophosphates may cause serious life-threatening conditions, such as an initial acute cholinergic crisis and intermediate syndrome. Each of these conditions has a potential for respiratory failure requiring ventilatory support. For this reason, it is very important to recognize them early, especially to institute appropriate management. The diagnosis of organophosphate poisoning is based essentially on a clinical assessment, followed by laboratory examinations. Sometimes the diagnosis may be difficult, as in case 1, identified initially as brainstem stroke. However, if neurological syndromes associated with organophosphate poisoning are well known, they can easily be distinguished from other conditions that resemble them. Two cases displayed the symptoms and signs of intermediate syndrome; however, one case (no. 2) did not have severe poisoning on admission but needed artificial ventilation. Each case recovered completely from organophosphate poisoning as a result of early diagnosis and appropriate therapy. Therefore, we would like to describe the clinical and laboratory features of these syndromes, observed in three interesting cases, and to emphasize the importance of early and accurate diagnosis for the appropriate management of acute organophosphate poisoning.     

Inadequate assessment of the airway and ventilation in acute poisoning. a need for improved education?

Aims and objectives: To analyse the initial management of acute poisoning patients, and whether respiratory morbidity was related to inadequate assessment of airway and ventilation. Methods: A retrospective analysis of the assessment and resuscitation of a group of acute poisoning patients, as documented in the clinical records. Subjects and setting: Forty one patients admitted to either Intensive Care or Coronary Care Units in a UK teaching hospital with a diagnosis of acute poisoning, between 12 January 1997 and 21 January 1998. Standards: Advanced Life Support Guidelines were used to compare initial assessment. Criteria for intubation and ventilation described by Gentleman was used as the standard for intubation. Results: Thirty seven patients had documented Glasgow Coma Scales at the time of admission, 27 were managed appropriately; one exhibited signs of aspiration. Ten patients were judged to be managed inappropriately; six exhibited clinical signs of aspiration. Four patients had unidentified Glasgow Coma Scales. Conclusions: Increased emphasis on ‘Airway and Breathing’ remains necessary in medical education. Regional recommendations for the management of acute poisoning require ‘intubation guidelines’. Appropriate ward settings for monitoring such patients may pre-empt the onset of major respiratory problems.     

Diazepam Inhibits Organophosphate-induced Central Respiratory Depression

OBJECTIVES: Current evidence suggests that mortality from acute organophosphate (OP) poisoning is partially mediated through central nervous system (CNS) respiratory center depression (CRD). However, the exact mechanism of OP-induced CRD is unknown. In these studies, the authors investigated the hypothesis that OP-induced CRD is the result of overstimulation of CNS respiratory centers. METHODS: Wistar rats received prophylaxis with either normal saline (controls), atropine, the peripherally acting anticholinergics glycopyrrolate (GLYC), ipratropium bromide (IB), or the CNS respiratory center attenuator diazepam. To determine if a dual CNS/peripheral cholinergic mechanism is responsible for animal death, two additional groups received combination treatment with diazepam plus either IB or GLYC. All treatments were completed 5 minutes before OP with subcutaneous dichlorvos. Differences in 10-minute and 24-hour mortality were assessed by the Fisher exact test. RESULTS: Dichlorvos poisoning resulted in profound fasciculations without obvious seizure in all cohorts. In controls and animals treated with peripherally acting anticholinergics, fasciculations were followed by sedation and respiratory arrest (0% 10-minute survival in all cohorts). In contrast, pretreatment with either atropine or diazepam significantly improved 10-minute survival (100% and 44%, respectively). Although GLYC or IB afforded no protection when given alone, when delivered in conjunction with diazepam, the combination significantly improved survival (both groups 88% at 24 hours), suggesting a dual CNS/pulmonary muscarinic mechanism of lethality. CONCLUSIONS: The central respiratory depressant diazepam paradoxically attenuates organophosphate-induced respiratory depression, and when combined with peripherally acting anticholinergic agents, reduces mortality in a rat model of severe acute OP poisoning.     

Predicting outcome using butyrylcholinesterase activity in organophosphorus pesticide self-poisoning

BACKGROUND: The usefulness of a low butyrylcholinesterase (BuChE) activity on admission for predicting severity in acute organophosphorus (OP) insecticide poisoning has long been debated. Previous studies have been confounded by the inclusion of multiple insecticides with differing inhibitory kinetics. AIM: We aimed to assess the usefulness of admission BuChE activity, together with plasma OP concentration, for predicting death with two specific organophosphorus insecticides. DESIGN: A prospective cohort of self-poisoned patients. METHODS: We prospectively studied 91 and 208 patients with proven dimethoate or chlorpyrifos self-poisoning treated using a standard protocol. Plasma butyrylcholinesterase activity and OP concentration were measured on admission and clinical outcomes recorded. RESULTS: The usefulness of a plasma BuChE activity <600 mU/ml on admission varied markedly--while highly sensitive in chlorpyrifos poisoning (sensitivity 11/11 deaths; 100%, 95% CI 71.5-100), its specificity was only 17.7% (12.6-23.7). In contrast, while poorly sensitive for deaths in dimethoate poisoning [12/25 patients; 48%, (27.9-68.7)] it was reasonably specific [86.4% (75.7-93.6)]. A high OP concentration on admission was associated with worse outcome; however, a clear threshold concentration was only present for dimethoate poisoning. CONCLUSION: Plasma BuChE activity on admission can provide useful information; however, it must be interpreted carefully. It can only be used to predict death when the insecticide ingested is known and its sensitivity and specificity for that insecticide has been studied. Plasma concentration of some OP insecticides predicts outcome. The development of rapid bedside tests for OP detection may aid early assessment of severity.     

Outcomes of morbidly obese patients requiring mechanical ventilation for acute respiratory failure

OBJECTIVE: To examine the outcomes of morbidly obese patients with acute respiratory failure treated with mechanical ventilation. DESIGN: Retrospective study. SETTING: A 14-bed medical intensive care unit in an 800-bed university-based hospital. PATIENTS: A total of 50 morbidly obese subjects with acute respiratory failure requiring ventilatory assistance. INTERVENTIONS: None. MEASUREMENTS: Arterial blood gas measurements, intubation rate, days of mechanical ventilation, intensive care unit length of stay, hospital length of stay, and mortality. RESULTS: From January 1997 to December 2004, 50 morbidly obese patients with acute respiratory failure were treated with mechanical ventilation. Invasive mechanical ventilation was implemented in 17 patients with a mean body mass index of 53.2 +/- 12.2 kg/m2. A total of 33 patients were treated with noninvasive ventilation (NIV), of which 21 avoided intubation (NIV success) and 12 required intubation (NIV failure). Mean body mass index for the NIV success group was significantly less than for the NIV failure group (46.9 +/- 8.9 and 62.5 +/- 16.1 kg/m2, respectively, p = .001). Acute Physiology and Chronic Health Evaluation II scores were similar for patients treated with invasive and noninvasive ventilation. Significant improvements in pH and Paco2 were noted for the invasive mechanical ventilation and NIV success groups. No improvements in gas exchange were noted in the NIV failure group. Of patients treated with NIV, 36% required intubation. Hospital mortality for the invasive ventilation and NIV failure groups was increased. CONCLUSION: The type of ventilatory assistance may influence clinical outcomes in morbidly obese patients with acute respiratory failure.     

Prognostic value of serial serum cholinesterase activities in organophosphate poisoned patients

Objectives

Organophosphate (OP) poisoning is a worldwide concern. Several factors have been identified to predict outcomes of OP poisoned patients. This study focuses on the relationship between the trend in Serum cholinesterase (SChE) activity and its clinical outcome in acute OP poisoned patients.

Methods

We retrospectively reviewed the medical records of all adult acute OP poisoned patients that visited the Emergency Department from 2000 to 2006. These patients were divided into two groups: the deceased patients as the sample group and all others as the control group. We collected data on the following: demographical factors, poisoning history, clinical manifestation, Glasgow Coma Scale (GCS), APACHE II score, all SChE data within 48 hours, hourly 2-PAM dosage, intubation, and mortality. Chi-Square test then examined the relationship between the trend of SChE activity and mortality.

Results

86 patients were enrolled. Follow-up measurements of SChE activity within 48 hours of poisoning were available in 50 cases. Among these, eight patients died. We found no significant difference between the sample and control groups on initial SChE activity, time interval to initial SChE data, and hourly 2-PAM dosage. The sampled group possessed a worse GCS score, lower systolic blood pressure, and a higher APACH II score. Increase patient mortality rates associated with the absence of elevating SChE activity within 48 hours of poisoning. (P = .006, odds ratio:11).

Conclusions

We propose that the absence of elevating SChE activity level within 48 hours of poisoning appears to associate with higher mortality in acute OP poisoned patients.     

Coumaphos Intoxications Mimic Food Poisoning

Abstract

Reports of food poisoning caused by pesticide-contaminated food are rare in the medical literature. In this paper, we report six patients who suffered food poisoning in two separate episodes in which the pesticide coumaphos was apparently misused as a food flavoring. These six patients presented not only the general manifestations of gastroenteritis, but also some unusual extraintestinal symptoms. These included cholinergic overactivity (miosis, urinary incontinence and hypersalivation) that led us to suspect organophosphate intoxication. This diagnosis was confirmed by serial changes in RBC cholinesterase and pseudocholinesterase activity, and by the presence of coumaphos in the contaminated food. Of the six patients, one was dead on arrival. Another patient developed progressive respiratory failure and required mechanical ventilation. The mortality rate among our cases was 16.7%. Since the coumaphos was apparently added to food during cooking, its toxic effects do not appear to be mitigated by heating. When food poisoning cases present with both gastroenteritis and unusual autonomic symptoms, the autonomic syndromes will aid in the diagnosis and management of these critically ill patients.     

Noninvasive vs invasive ventilation in COPD patients with severe acute respiratory failure deemed to require ventilatory assistance

Objective To determine whether non-invasive ventilation (NIV) may be an effective and safe alternative to invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) meeting criteria for mechanical ventilation.Design and setting Matched case-control study conducted in ICU.Patients and intervention NIV was prospectively applied to 64 COPD patients with advanced ARF. Their outcomes were compared with those of a control group of 64 COPD patients matched on age, FEV₁, Simplified Acute Physiology Score II, and pH at ICU admission, previously treated in the same ICU with conventional invasive mechanical ventilation.Methods and results NIV failed in 40 patients who required intubation. Mortality rate, duration of mechanical ventilation, and lengths of ICU and post-ICU stay were not different between the two groups. The NIV group had fewer complications (P = 0.01) and showed a trend toward a lower proportion of patients remaining on mechanical ventilation after 30 days (P = 0.056). Compared to the control group, the outcomes of the patients who failed NIV were no different. Compared to the patients who received intubation, those who succeeded NIV had reduced mortality rate and lengths of ICU and post-ICU stay.Conclusions In COPD patients with advanced hypercapnic acute respiratory failure, NIV had a high rate of failure, but, nevertheless, provided some advantages, compared to conventional invasive ventilation. Subgroup analysis suggested that the delay in intubation was not deleterious in the patients who failed NIV, whereas a better outcome was confirmed for the patients who avoided intubation.     

Glasgow Coma Scale Score and QTc Interval in the Prognosis of Organophosphate Poisoning

OBJECTIVES: The aim of this study was to assess the applicability of the Glasgow Coma Scale (GCS) score and the Q-T interval corrected for heart rate (QTc interval) in predicting outcome and complications in patients with organophosphate (OP) poisoning. METHODS: This prospective, observational study included 65 patients older than 18 years. In the out-of-hospital setting, the end-tidal carbon dioxide (ETCO2), oxygen saturation (SaO2), QTc interval, and GCS score were monitored in each patient. A statistical comparison was then made between the group with respiratory failure and the group without this complication. RESULTS: The group with complications had significantly different values of measured parameters--a longer QTc interval and a lower GCS score, a higher number of intubations, and worse outcomes (p < 0.05). The two measures, GCS score and QTc interval, have been shown to be equally good in predicting respiratory failure and hospital mortality in patients with OP poisoning. CONCLUSIONS: In the initial out-of-hospital care of patients with OP poisoning, it is essential to monitor QTc interval and GCS score. These measures help with prognosis, and may suggest when to initiate precautions to prevent complications (i.e., respiratory failure). The simplicity and promptness of these methods allow providers to perform early and effective triage.     

Survival Pattern in Patients with Acute Organophosphate Poisoning Receiving Intensive Care

Background. Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. Objective. To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. Methods. Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. Results. During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1–27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO₂ of > 40% to maintain a SpO₂ of > 92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. Conclusion. Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One‐third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO₂ > 40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU.     

Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis: benefits of intensive care?

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a cause of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD) treated with corticosteroids. For these patients admission in intensive care unit (ICU) is often required for life-support and mechanical ventilation. Whether this approach improves outcome is unknown. DESIGN AND SETTING: Retrospective study in a university hospital intensive care unit. PATIENTS: Between November 1993 and December 1997, 23 COPD patients were admitted in our ICU and received antifungal agents for possible IPA. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical features and the outcome were reviewed. Diagnosis of IPA was classified as confirmed (positive lung tissue biopsy and/or autopsy) or probable (repeated isolation of Aspergillus from the airways with consistent clinical and radiological findings). Among the 23 patients treated for Aspergillus, 16 fulfilling these criteria for IPA were studied. Steroids had been administered at home to all patients but one and were increased during hospitalization in all. Twelve patients suffered a worsening of their bronchospasm precipitating acute respiratory failure. During ICU stay all patients required mechanical ventilation for acute respiratory failure. Although amphotericin B deoxycholate was started when IPA was suspected (0.5-1.5 mg/kg per day), all patients died in septic shock (n = 5) or in multiple-organ failure. CONCLUSIONS: The poor prognosis of intubated COPD patients with IPA, in spite of antifungal treatment suggests that further studies are required to define the limits and indications for ICU management of these patients.     

预见性气管插管治疗急性重度药物中毒临床观察

目的:探讨重度药物中毒患者的气管插管时机对治疗效果的影响。方法:对57例出现呼吸困难的重度药物中毒患者,进行密切观察,在常规治疗的基础上,随机分为预见性气管插管组与延时气管插管组;以并发症发生情况及抢救成功率进行统计学处理,比较两组患者的抢救效果。结果:各种并发症发生情况两组比较P>0.05差异无统计学意义,可能与中毒的量及中毒时间有关;不同时机气管插管抢救成功率两组比较P<0.05,有一定的可比性。结论:预见性气管插管有助于重度药物中毒患者的抢救,气管插管最佳时机为呼吸衰竭早期。     

血清淀粉酶测定在急性有机磷农药中毒中的临床意义

目的 探讨急性有机磷农药中毒时急性呼吸衰竭与非急性呼吸衰竭时血清淀粉酶的变化规律及临床意义.方法 采用酶法测定76例急性有机磷农药中毒患者(急性呼吸衰竭24例,非急性呼吸衰竭52例)的血清淀粉酶.结果 76例急性有机磷中毒患者中24例发生呼吸衰竭者血清淀粉酶显著高于52例未发生呼吸衰竭者血清淀粉酶(P＜0.05).结论 急性有机磷农药中毒时血清淀粉酶越高,提示中毒程度越深,发生呼吸衰竭的可能性越大.     

Controlled trial of oronasal versus nasal mask ventilation in the treatment of acute respiratory failure

OBJECTIVE: Noninvasive positive pressure techniques such as continuous and bilevel positive airway pressure avoid intubation and its attendant complications in selected patients with acute respiratory failure. However, mask intolerance remains a common cause for failure of noninvasive ventilatory techniques. The aim of our study was to assess patient tolerance of oronasal vs. nasal mask ventilation in acute respiratory failure. DESIGN: Randomized, controlled trial. SETTING: Emergency department or intensive care units at a university hospital. PATIENTS: Seventy patients with acute respiratory failure as evidenced by clinical or blood gas criteria. INTERVENTIONS: Patients randomly received either a disposable nasal or an oronasal mask (Respironics, Pittsburgh, PA) when they met study criteria. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were randomized into each arm of the study; most of the patients had acute cardiogenic pulmonary edema (48.6% of the nasal mask group and 42.8% of the facial mask group) or chronic obstructive airway disease (34.3% of the nasal mask group and 31.4% of the facial mask group). Baseline clinical characteristics of the two groups of patients were similar. Heart and respiratory rates and blood gases improved similarly for patients in both mask groups. Rates of intubation were also similar (eight in each group). However, mask intolerance was significantly higher in the nasal than the oronasal mask group (12 vs. 4, respectively, p=.023). Four patients in the nasal (11.4%) and two in the oronasal mask group (5.7%) died later during the hospitalization. The overall success rate tended to be greater in the oronasal (65.7%) than the nasal group (48.6%), but the difference was not statistically significant. CONCLUSION: Although both masks performed similarly with regard to improving vital signs and gas exchange and avoiding intubation, the nasal mask was less well tolerated than the oronasal mask in patients with acute respiratory failure.     

Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain–Barré syndrome

Objective Invasive mechanical ventilation is required in 30% of patients with Guillain–Barré syndrome (GBS) and is associated with pneumonia and increased mortality. Our objective was to determine the incidence, characteristics, outcomes, and risk factors of pneumonia in GBS patients receiving mechanical ventilation.Design and setting Study of a prospective database in an intensive care unit of a university hospital.Patients The study included 81 patients who required intubation for GBS. Neurological findings, vital capacity, and signs of respiratory distress were recorded at admission and at intubation. A score predicting the risk of intubation (0–4) was calculated for each patient. Pneumonia was diagnosed based on predefined criteria and retrospectively confirmed by two observers. Early-onset pneumonia was defined as pneumonia diagnosed within 5 days after intubation.Measurements and results Mean vital capacity was 57 ± 22% of predicted at admission and 33 ± 11% at intubation. Pneumonia developed in 63 patients (78%), including 48 with early-onset pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower risk of intubation (score < 2), and time from admission to intubation longer than 2 days were associated with early-onset pneumonia. Time from admission to intubation was the only independent predictor in the multivariate logistic regression model.Conclusions Early-onset pneumonia is a common and severe complication that is related to aspiration in patients with GBS. Delaying intubation may increase the risk of early-onset pneumonia.     

急性毒鼠强中毒71例分析

目的:为提高急性毒鼠强中毒的认识和抢救水平.方法:急性毒鼠强中毒患者71例,按职业性接触中毒和非职业性中毒(胃肠道途径)分类,分析救治措施和进行疗效统计.结果:非职业性(胃肠道途径)中毒者多在口服后10min至2h发病,主要表现为头昏、乏力、恶心、呕吐、重症者表现为抽搐(50例)、伴昏迷(23例)、休克(7例)、心律失常(24例)、急性肺水肿(14例)、呼吸衰竭(21例)和咯血(1例),服毒量越多,病情越重,职业中毒者症状均较轻;本组有14例死亡,病死原因均为呼吸衰竭,病死率与服毒量有关,青少年及老年人病死率高于青中年患者.结论:毒鼠强毒性强、可致多器官损害,重症患者病死率高,主要死亡原因为呼吸衰竭,救治过程中应强调早期彻底清除毒物,重症者宜早期予人工支持呼吸.     

Two-level non-invasive positive pressure ventilation in the initial treatment of acute respiratory failure in an emergency department.

There are few data on the use of two-level non-invasive positive pressure ventilation (two-level nIPPV) in the initial treatment of severe acute respiratory failure in emergency departments (ED). In a prospective, non-randomized, pilot study, we assessed (1) the feasability of this method in an ED, (2) its effect on clinical and laboratory data, and (3) its effect on the need of intubation and the final outcome of patients. During a 1-year period all eligible patients admitted for acute respiratory failure, with absence of improvement after periods of specific classic treatments, were included in the study. Each patient received a specific classic treatment and two-level nIPPV with a two-level positive pressure ventilator through a face mask. We recorded parameters on admission, after 15 and 45 minutes of nIPPV and at the end of nIPPV. Sixty-two patients were included: 29 with acute pulmonary oedema (APO), 16 with acute exacerbation of chronic obstructive pulmonary disease (COPD), four with asthma, and 13 with various diseases. In the APO-group, we observed a statistically significant improvement of respiratory and pulse rates, diastolic blood pressure, pH, PaCO2 and SaO2. In acute exacerbation of COPD, we observed only a statistical improvement of respiratory and pulse rates without any significant change of PaCO2 and pH. In the two other groups, there was a clinical, gasometric and haemodynamic improvement in all patients. Four patients were intubated and 10 died, but none in the ED or in the first 24 hours after hospital admission. We were able to institute two-level nIPPV for severe acute respiratory failure in an ED without complications. Its addition to the rest of classic specific treatment seems to bring about a rapid improvement of various clinical and laboratory parameters in most patients. We found no deleterious effect of nIPPV when implemented for short periods of time in the emergency department setting.     

Early Death Due to Severe Organophosphate Poisoning Is a Centrally Mediated Process

OBJECTIVE: To distinguish whether early death from severe organophosphate (OP) poisoning with dichlorvos is mediated through peripheral or central nervous system (CNS) actions. METHODS: Wistar rats (n = 72) were randomized to pretreatment with either: normal saline (controls), peripheral anticholinergics (glycopyrrolate [low, medium, or high dose] or nebulized ipratropium bromide), or CNS + peripherally acting anticholinergics (diphenhydramine, nebulized atropine, or injected atropine). All treatments were given prior to a subcutaneous injection of 25 mg/kg dichlorvos (n = 8 per group). Survival was assessed at 10 minutes (early death) and 24 hours (delayed death). Kaplan-Meier (95% confidence intervals [95% CIs]) and chi-squared analysis was then performed to determine differences between treatments. RESULTS: Regardless of treatment, all animals exhibited profound nicotinic effects (fasciculations) without obvious seizures within 2 minutes of poisoning. In rats pretreated with peripherally acting agents, the fasciculations were rapidly followed by reduced motor activity, sedation, and death. Mortality at 10 minutes for saline controls, glycopyrrolate, and ipratropium was 88%, 96%, and 100%, respectively. The single control animal surviving beyond 10 minutes went on to develop peripheral cholinergic manifestations, including hypersalivation, urination, and defecation. Only one of 24 animals treated with injected atropine, nebulized atropine, or diphenhydramine died during the early phase of poisoning; all others survived to 24 hours (p < 0.01). CONCLUSIONS: Death in acute, severe OP poisoning is prevented by pretreatment with anticholinergic agents that cross the blood-brain barrier, but not by agents with only peripheral actions. Early death due to OP poisoning appears to be a centrally mediated process.