American Journal of Emergency Medicine (2008) 26, 721-730

Acid-base interpretation as a predictor “>Correspondence

Acidosis is a life-threatening condition regardless of the underlying condition

To the Editor,

Firstly, thanks to Liu et al [1] for their article about the effect of acidosis on mortality in organophosphate poison- ings. However, I have some concerns on the hypothesis of the article.

There are 2 hypotheses needed to be constructed during the beginning of a clinical study, H₀ and H₁. H₀ hypothesis is the foresight that claims that the difference between 2 groups is found to be a run of luck, which means there is no difference between the 2 groups. An H₁ hypothesis claims that the difference is not found, accidentally supporting that the difference is real. Liu et al [1] tested the hypotheses that acidosis is a remark of mortality in organophosphate poisonings, H₁ hypothesis. However, the problem exists by the H₀ hypothesis. Acidosis is known to be a potent depressor of cardiovascular system. As known, the existence of acidosis is a life-threatening condition regard- less of the underlying pathology. H₀ hypothesis collapsed in the beginning of the study, which makes useless attempts to perform the study. If we accept that an opposite finding was found at the end of the study-that there was no difference between the patients with and without acidosis, would we claim that acidosis should be disregarded in organo- phosphate poisonings. Can we claim that acidosis is not a life-threatening condition? I think this is unlikely to be a rational suggestion.

As a conclusion, acidosis is a life-threatening condition regardless of the underlying condition. The clinical question arises if a Scientific study should test both the H₀ and H₁ hypotheses. If one of them is known before the study, this may cause unnecessary attempts.

Acknowledgment

This study was supported by Akdeniz University Foundation.

Cenker Eken MD Department of Emergency Medicine Akdeniz University Faculty of Medicine

07059 Antalya/Turkey E-mail address: [email protected]

doi:10.1016/j.ajem.2008.03.038

Reference

[1] Liu JH, Chou CY, Liu YL, Liao PY, Lin PW, Lin HH, et al. Acid-base interpretation can be the Predictor of outcome among patients with acute organophosphate poisoning before hospitalization. Am J Emerg Med 2008;26:24-30.

Acid-base interpretation as a predictor of outcome in acute organophosphate poisoning

To the Editor,

In their recent publication, Liu et al [1] reported that the presence and type of acidosis before hospitalization can be an accurate predictor of 30-day mortality in patients with acute organophosphate (OP) poisonings. We are concerned that several limiting factors exist that undermine the validity of this conclusion.

There are many complexities of patients with OP poisoning that make diagnosis, management, and treatment extremely challenging. Liu et al [1] use the presence of three nonspecific indicators of cardiovascular failure: (1) cardiogenic pulmonary edema; (2) electrocardiogram abnormalities including pro- longed QTc, ST-T changes, or conduction defects; and (3) cardiac arrhythmias. In defining respiratory failure, they rely solely on the use of mechanical ventilation regardless of whether it was instituted to correct hypoxia, hypercapnia, or for airway protection. Prospective differentiation of pulmonary edema, bronchorrhea, bronchospasm, and hydrocarbon pneu- monitis provide challenges to the clinician and can oftentimes only be determined by invasive monitoring and further testing. Attempting to determine these disease processes retrospec- tively in the absence of any further diagnostic testing is nearly

0735-6757/$ - see front matter (C) 2008

722 Correspondence

impossible. In addition, simply stating that a patient had bradycardia before any respiratory compromise does not imply that a patient’s death was due to Cardiovascular causes. Furthermore, by using 30-day mortality as a primary outcome, many significant and common complications that increase mortality such as ventilator and aspiration-associated pneu- monia, myocardial infarction, sepsis, and other mechanisms of further injury and death are ignored.

Many aspects of the management of these patients raise the question of whether these patients truly had a consequential ingestion and whether many of the patients were undertreated. The treatments utilized for acute organophosphate poisoning in this case series are both inconsistent and insufficient. The paper recognizes that not all patients received the same therapies, most having received both IV pralidoxime and IV atropine sulfate but several receiving only one of these 2 standard antidotes. With regard to the use of atropine, the patients in this study received 2 mg every hour, which is far less than current recommendations to administer 0.02 to

0.05 mg/kg IV, with a doubling of the dose every 5 minutes until control of secretions is established [2-4].

In addition, the doses of pralidoxime given were subther- apeutic. In this study, only 4 to 6 g of pralidoxime was given daily with continuous intravenous infusion “as long as possible” [1]. Although daily doses of 6 mg/day are commonly used throughout Asia, they fall far below recommended guidelines [5]. The World Health Organization recommends a 30-mg/kg loading dose followed by intravenous infusions of at least 8 mg/kg per hour which, for a 50-kg patient, would amount to a daily dose of about 11 g [6]. In addition, in one recent study, high-dose continuous pralidoxime infusions using a 2-g loading dose followed by 1-g/h Continuous intravenous infusions for 48 hours (26 g/day) significantly reduced mortality as well as the need for intubation and ventilator support, development of muscle weakness and pneumonia, and need for atropine during the first day of treatment [7]. Based on the Treatment regimen used by Liu et al [1], many patients were likely to have received inadequate doses of pralidoxime and, more importantly, atropine.

Thus, although the authors attempted to simplify

predictors of outcome in organophosphate exposure, we believe that patients with consequential ingestions are complicated by many factors other than simple acid-base disturbances. Although acid-base disturbances may play a role in the toxicity of organophosphate exposures, we believe the clinical status of the patient is a much more reliable indicator of mortality.

Joseph Shin MS4 NYU School of Medicine New York, NY 10016, USA

Nima Majlesi DO Department of Emergency Medicine North Shore University Hospital Manhasset, NY 11030, USA

Robert Hoffman MD

Department of Emergency Medicine

NYU School of Medicine New York, NY 10016, USA

doi:10.1016/j.ajem.2008.03.037

References

1. Liu JH, et al. Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospita- lization. Am J Emerg Med 2008;26:24-30.
2. Johnson MK, et al. Evaluation of antidotes for poisoning by organophosphorus pesticides. Emerg Med 2000;12:22.
3. Eddleston M, Roberts D, Buckley N. Management of severe organophosphorus pesticide poisoning. Crit Care 2002;6:259.
4. Eddleston M, Singh S, Buckley N. Acute organophosphorus poisoning.

Clin Evid 2003;9:1542.

1. Eddleston M, et al. Oximes in acute organophosphates pesticide poisoning: a systematic review of clinical trials. QJM 2002;95: 275-83.
2. Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev 2003;22:165-90.
3. Pawar KS, et al. Continuous pralidoxime infusion versus repeated Bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006;368:2136-41.

Reply to “Acidosis is a life-threatening condition regardless of the underlying condition” and “Acid-base interpretation as a predictor of outcome in acute organophosphate poisoning”

To the Editor,

We really appreciate Dr Eken’s inspiring feedback about our article entitled “Acid-base interpretation can be the predictor of outcome among patients with acute organo- phosphate poisoning before hospitalization.” In regard to the null hypothesis, H1, that acidosis is associated with mortality regardless of the underlying condition, we agreed with Dr Eken’s opinion that acidosis is a life-threatening condition. However, quite a few studies have shown that acidosis may not be associated with mortality in certain groups of patients[1-4], suggesting the need to study the influence of acidosis in patients with difference underlying conditions. organic phosphate intoxication is a medical condition that may be related to variety of acid-base disturbance, for example, respiratory acidosis due to Respiratory insufficiency, metabolic acidosis due to shock, or the mixed ones. We therefore hypothesized that patients with different types of acid-base disturbance after organic phosphate intoxication have different mortality rates and morbidity, which is our null hypothesis, H0.

We also appreciate Dr Shin’s comments about our

article. Regarding the treatment of acute organophosphate in our country, the atropine dosages were as follows: