Letter to the Editor: “Use of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning is advancing”

To the Editor:

We have read with interest the comments from Roberts et al., entitled “Plasma alkalization for acute organophosphorous poisoning-is it a reality in the developing world?” regarding our previous publication, “Effects of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning” (Clin Toxicol 2005; 43:571–574).

The Medical Toxicology Center of Mashhad has been involved in the investigation of the therapeutic effects of sodium bicarbonate in acute organophosphorous pesticide poisoning forover a decade. The patients have been under our direct care and we have had no problems obtaining the approval of the University ethics committee and the informed consent of the patients/relatives. Our research team on this subject has recently been extended and three other colleagues are now involved in the study of more cases, in full detail, pertaining to the efficacy and safety of sodium bicarbonate in OP pesticide poisoning.

We would first like to thank Roberts et al. for their comments and would appreciate their efforts to undertake the study in Sri Lanka. Our views on their title are as follows:

1. Alkalization is for all of the blood, not just plasma.

2. Acute organophosphorous poisoning also includes chemical warfare agents such as Sarin, Soman, and Tabun. We have studied the effects of NaHCO3 only on OP pesticides, although both are anti-cholinesterase agents.

3. The answer to their question of reality in the developing world is yes, provided facilities use it properly.

We agree with the result of the systematic review that Roberts et al. performed through the Cochrane Collaboration, which indicated there was insufficient evidence to recommend the routine use of blood alkalization in acute OP pesticide poisoning. This is the reason that we are now investigating more cases.

Regarding the method and regimen of alkalization to optimally induce and maintain the target arterial pH, we first applied the constant low dose of sodium bicarbonate (loading doses 3 mEq/kg, followed by constant infusion of 2–3m/eq/kg/24 hours) as recommended by Wong (1), but it did not result in sufficient alkalization, as the arterial blood pH did not increase significantly (2). We thus aimed to study high doses of sodium bicarbonate; a loading dose of 5mEq/kg over one hour followed by 5–6 mEq/kg daily until recovery/death to achieve and maintain arterial pH between 7.45 and 7.55 (3,4). With this regimen, arterial blood pH increased significantly (p<0.001) from 7.24±0.12 on admission to 7.48±0.02 during treatment. The highest recorded arterial blood pH was 7.54.

Our clinical staff and even the interns have no problem in taking arterial blood using insulin syringes. The severely poisoned patients who transferred to ICU received arterial lines and thus sampling was even easier. Arterial blood gas analyzers (AVL 995) are available in the Emergency Toxicology Laboratory located beside the poisoned treatment ward and in the emergency Clinical Biochemistry Laboratory of the hospital. Based on our experience, estimation of arterial blood pH and gases, required two to six times a day for the study, was overused by the junior doctors not only for the adjustment of pH in this study, but also for most poisoned patients. Fortunately we have had no serious problems encountering arterial blood sampling.

Regarding the safety of blood alkalization with intravenous sodium bicarbonate, we were aware of the risks and thus did not administer intravenously. As stated in the methodology of the published article, 50 ml of 7.5% of sodium bicarbonate was diluted 1:5 in 5% dextrose solutions before infusion. We used 3 to 4 liters of fluid daily and thus no fluid overdose occurred, and there has been no matter of forced alkaline diuresis. Therefore, overload complication such as pulmonary edema was not higher in the sodium bicarbonate cases than in the controls.

Based on our experience over the years, for the adjustment of arterial blood pH between 7.45 and 7.55, after infusion of the loading dose of 5 mEq/kg body weight of the patient in one hour, three 50 ml vials of sodium bicarbonate in 1 liter of 5% dextrose was infused in 6–8 hours. Depending on the arterial blood pH measurement near the end of this infusion, adjustment of the next dose was made (2–4 vials in one liter of 5% Dextrose). The same procedure was repeated at the end of the third liter infusion. This has been the routine adjustment for the arterial pH of patients treated in the ward. For the severely poisoned patients treated in the ICU, more close observation and adjustment were performed. The results of safety issues were not reported in the original article due to space management, but are summarized here. To avoid hypokalemia, 20 mEq potassium chloride was added to each 50 ml vial of sodium bicarbonate. Serial estimation of serum calcium in the pilot study several years ago did not reveal hypocalcemia. However, serum calcium together with other electrolytes (Na, K, Cl, and Mg) and biochemical tests (urea, creatinin, blood sugar, lipase, amylase, CPK, LDH, ALT, and AST) were performed daily. We did not find any significant biochemical abnormalities, except for the severely intoxicated patients who died in the ICU due to organ failure. As already stated, the maximum arterial blood pH was 7.54 and thus had no record of over alkalization. Hypercarbia was also not found in our patients.

In our new study on 65 patients who were treated with the high doses of sodium bicarbonate, alkalosis was recorded only in two patients and was respiratory rather than metabolic. The safety data on these patients are summarized in Table 1.

Table 1. Safety data for blood alkalization of organophosphorus poisoning in 65 patients

Variables	+	−	%
pH>7.55	2	63	3.1
pH>7.45	57	8	87
PCO2>55 mm Hg	0	65	0
Serum Na >145 mEq/L	0	65	0
Serum K<3.5 mEq/L on admission	5	60	7.7
Serum K<3.5 mEq/L during treatment	0	0	0
Cases required adjustment for arterial blood pH	10	55	15.4

Most of our patients with OP pesticide poisoning are young with normal renal function. Each day the kidneys filter about 4320 mEq of bicarbonate and under normal conditions, almost all of this is reabsorbed from the tubules, thereby conserving the primary buffer system of the extra cellular fluids. When there is a reduction in the extra cellular fluid hydrogen ion concentration (alkalosis), the kidneys fail to re-absorb all of the filtered bicarbonate, thereby increasing the excretion of bicarbonate. The increase in urinary bicarbonate excretion serves to eliminate excess bicarbonate from the blood and to rapidly restore the plasma bicarbonate concentration to normal (5).

The kidney's bicarbonate excretory capacity is enormous, and a sustained rise in plasma bicarbonate concentration is so efficient that in individuals taking bicarbonate in amounts as high as 20 mEq/kg per day for several weeks, only a trivial rise in plasma bicarbonate is observed (6). These are the reasons that we have not observed any serious problems or complications.

In conclusion, we hope the above information, explanations, and clarifications will help our respected colleagues of SACTRC to carry out this research in Sri Lanka. However, differences in the race, culture, and socioeconomic conditions of the patients in Sri Lanka and the effects of environment may affect the result. We are thus very interested to see their results in the coming years.