The use of isotonic sodium chloride in the early treatment of cholera diarrhea: the Peruvian

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1 Journal of Wilderness Medicine 4, (199) ORIGINAL ARTICLE The use of isotonic sodium chloride in the early treatment of cholera diarrhea: the Peruvian. expenence M. VARGAS, MOl, L. HUICHO, MOl, V. SALCEDO, M0 2 and E. MONGE, M0 JDepartamento de Ciencias Fisiol6gicas, Laboratorio de,biofisica, Universidad Peruana Cayetano Heredia, Lima, Peru 2Hospital Central de la Fuerza Aerea Peruana, Lima, Peru Servicio de Gastroenterologia, Hospital Nacional Daniel Alcides Carrion, Callao, Peru Due to the limited supply in Peru of polyelectrolitic solutions recommended for the initial treatment of cholera diarrhea, a massive amount of isotonic sodium chloride solution was used during the recent cholera epidemic. This treatment proved adequate based on the low mortality rate, which compared favorably with international mortality rate reports. A preliminary observation of six adult Peruvian patients hospitalized with hypovolemic shock and metabolic acidosis secondary to cholera diarrhea showed remission of hypovolemic manifestations and significant improvement of serum bicarbonate, pco z, and base excess after rapid intravenous infusion of a solution of isotonic sodium chloride. This intravenous solution seems adequate as the initial intravenous fluid for patients with severe cholera, as a logical alternative to currently recommended polyelectrolitic solutions containing bicarbonate or lactate. Key words: cholera, hypovolemic shock, metabolic acidosis, intravenous rehydration, bicarbonate, diarrheal disease Introduction A cholera epidemic began in the coastal cities of Peru in January Up to May 1991, cases were reported, with an admission rate of 9% (72140 cases) and an overall case-fatality rate of 0.82% (157 cases) [1,2]. A substantial proportion of patients with cholera show severe dehydration and/or hypovolemic shock and metabolic acidosis, requiring vigorous intravenous fluid replacement. Current management guidelines recommended by WHO [] for such severely affected patients include intravenous administration of polyelectrolitic solutions containing either lactate or bicarbonate, all of which have, with minimal differences, the following composition (mmon- l ): sodium, 154; potassium, 1.5, chloride, 99; bicarbonate, 48 (or bicarbonate, 20 plus lactate, 28). The magnitude of the epidemic forced the Peruvian authorities to declare an emergency in the health sector. This situation revealed several limitations, one of them being the scarcity of Ringer's Lactate and other intravenous solutions containing bicarbonate, so that the logistic capacities were often surpassed by the excessive number of patients requiring inpatient management. Because of this, physicians were often forced to administer between 4-8 I of solutions of isotonic sodium Chapman & Hall

2 Isotonic sodium chloride in the early treatment of cholera diarrhea 6 chloride (sodium chloride 0.9%) without bicarbonate as the only initial replacement fluid to the majority of severely affected patients. Although we do not have precise national numbers, far more than 70% of inpatients from hospitals of the Ministry of Health received normal saline infusions. In spite of this, the national case-fatality rate was less than 1% [4], which compared favorably with international death rate records. Neighboring countries such as Ecuador showed a national case-fatality rate of 2.42% [2], and at other latitudes, such as Zambia in Africa, overall figures up to 10% have been reported [5]. This suggests that the Peruvian treatment was adequate. In order to evaluate the possible aggravation of the bicarbonate deficit secondary to the use of large quantities of sodium chloride, we conducted a prospective, preliminary observational study in hospitalized patients with cholera who were initially treated with intravenous solutions of sodium chloride in water. Patients and methods Patients with diarrhea due to Vibrio cholerae El Tor attending the Emergency Ward of the Hospital Central de la Fuerza Aerea Peruana, Lima, Peru were enrolled. The study was carried out between 8 May 1991, and 10 June Patients were eligible if they met the following inclusion criteria: (1) age between 17 and 75 years old, (2) presence of hypovolemic shock and/or severe metabolic acidosis (ph :;; 7.20, and/or plasma bicarbonate :;; 10), and () cholera diagnosis subsequently confirmed by stool culture. Hypovolemic shock was defined and classified according to current recommendations [6], namely, presence of the following: non-palpable radial pulse or thready carotid pulse, systolic blood pressure :;; 80 mmhg, oliguria defined as urinary output below 0 mlh-1, tachypnea, and drowsiness, confusion, or unconsciousness. Exclusion criteria were: (1) patients without record of serial arterial blood gas analysis (baseline and immediately after rapid intravenous fluid replacement), (2) previous intravenous fluid therapy, and () presence of other concomitant causes of shock or metabolic acidosis. All patients were approached according to a protocol for critically ill patients approved by the Hospital Ethics Committee. During the study period, a total of 100 patients with presumptive diagnosis of cholera were admitted to the hospital, and diagnosis was confirmed by stool culture in 1 patients, who were the initially eligible. Ten patients were then excluded because of lack of basal arterial blood gas analysis, six because they had been referred from other institutions after unspecified intravenous fluid therapy, and nine because they had not yielded a second arterial blood gas analysis immediately after rapid saline intravenous infusion. Thus six patients met all inclusion criteria and were finally included. On enrollment, a baseline arterial blood gas analysis was performed by radial artery puncture to assess acid-base status. Immediately afterwards, the patients received an intravenous infusion of isotonic sodium chloride through an adequate peripheral intravenous catheter. The solution was infused over the course of two to three hours, to replenish an estimated loss of ten percent of body weight. Accordingly, the infusion rate was between 1.7 and.61h- 1 (see Table 1) and saline was administered as the only treatment until the patient was out of shock (systolic blood pressure above 80 mmhg, easily palpable radial pulse, return of consciousness) and urinating (urinary output above 0 mlh- 1 ). After the rapid volume replacement phase, a second blood sample was taken from the radial artery for ph and gas analysis, a 5% dextrose in saline solution was

3 64 Table 1. Principal clinical features of patients Vargas, Hincho, Salcedo and Monge Patient Age (years), sex Weight (kg) Diarrhea before admission (h) NaCI influsion* (I h- 1 ) Time to ORS** (h) Hospitalization (days) 72,M ,M ,F ,M ,M ,M *IV normal saline infusion as initial emergency treatment. **Interval between admission and adequate ORS tolerance. infused at a rate to match measured stool and urinary losses, and patients were promptly encouraged to drink the WHO/UNICEF oral rehydration solution (ORS) (concentrations of electrolytes in mmou- 1 of sodium, 90; potassium, 20; chloride, 80; citrate, 20; and glucose, 110). Criteria for ORS indication were patients out of shock, as defined above, and remission of profuse vomiting which would otherwise preclude oral rehydration. Results Details of clinical and laboratory findings are shown in Tables 1 and 2. At admission, all six patients had the following features of shock: non-palpable or thready pulse, systolic hypotension, tachypnea, drowsiness, confusion, or unconsciousness. Serum bicarbonate was ~ 10.9 mmoll- 1 in all subjects. In four patients, ph was below 7.25, while one had 7.29 and another 7.4. The patient with ph 7.4 had a serum bicarbonate of 8.0 and the patient with ph 7.29 had a serum bicarbonate of 7.. After rapid volume expansion with physiologic sodium chloride infusion, shock signs subsided in all patients. Details of ph, serum bicarbonate, base excess, pc0 2, and outcome are shown in Table. After normal saline infusion, all patients had levels of serum bicarbonate which were higher compared to entry levels (Fig. 1). Similarly, base excess and pc0 2 improved substantially, whereas the ph average, although higher, was not very different. Oral ingestion was withheld until four hours after admission. Adequate oral tolerance was delayed for much longer because of frequent vomiting (Table 1). The six patients survived and were discharged without complications. Discussiou Our results, albeit preliminary, suggest that in patients with hypovolemic shock secondary to cholera diarrhea, it may not be necessary to use intravenous fluids containing either lactate or bicarbonate. Once our patients were vigorosly treated with saline solution, the signs of shock subsided. Likewise, the manifestations of metabolic acidosis (e.g., acidotic respiration, as well as measured blood levels of pc0 2, bicarbonate, and base excess) improved clearly.

4 Isotonic sodium chloride in the early treatment ofcholera diarrhea 65 Table 2. Additional clinical and laboratory data before (upper line) and after (lower line) IV NaCI infusion Patient Blood pressure (mmhg) 70/0 80/50 70/0 60/40 80/50 60/40 90/60 110/80 90/50 110/70 110/80 110/60 Pulse rate (min-i) 94* 98* NP 120* 92* 108* * Respiratory rate (min-i) Urine output (ml h- I ) Anuric Anuric Anuric Anuric Anuric Anuric Consciousness Conf. Conf. Uncon. Conf. Drowsy Drowsy Alert Alert Drowsy Alert Conf. Alert Sodium (mmoll-') Potassium (mmoll- ' ) Creatinine (f!moll-') ND *Thready pulse NP: Non palpable pulse ND: Not done Conf.: confused Uncon.: unconscious Table. Acid-base status before and after saline infusion, as determined by arterial blood gas analysis Patient ph pc0 2 HC0 BE Before After Before After Before After Before After BE = base excess

5 66 Vargas, Hincho, Salcedo and Monge The cornerstone of severe cholera treatment is adequate fluid replacement, preferably with oral rehydration in mild and moderate cases. Rationale for such management is replacement of water and electrolytes losses. The watery stool in cholera is isotonic [7], containing usually (mmoll- 1 ): sodium, 15; potassium, 15; chloride, 100; and bicarbonate, 45. In severely affected patients, the intravenous fluid infusion is necessary and can be life-saving. There is consensus that polyelectrolitic solutions containing bicarbonate (or lactate, which is converted to bicarbonate in the liver), with similar electrolyte concentration to the above-noted stool composition, are the ideal solutions. In fact, WHO recommends the use of Ringer's Lactate for intravenous treatment of severely affected cholera patients []. The argument is that these solutions are both adequate in composition and commercially available. However, despite international support, we have seen a dramatic shortage of these solutions during this epidemic, even in the hospitals of Lima, the Peruvian capital. There are additional problems in the massive and rapid use of polyelectrolitic solutions. These are the elevated cost ($.45 per liter of normal saline vs $6.29 per liter of a standard polyelectrolitic solution, on the basis of current commercially available products), more elaborate industrial preparation, and potential risks of infusing polyelectrolitic solutions rapidly without adequate clinical and chemical controls, particularly in rural and jungle primary health care centers. In this regard, the use of bicarbonate in life-threatening metabolic acidosis is a hotly debated issue [8-10]. BICARBONATE (mmol/l) 16, , POST TREATMENT 8 6 PRE TREATMENT Patient -+- Patient 2 ---*- Patient --B- Patient 4 -*- Patient 5 -+ Patient 6 4 _~ +_ L l o TIME (min) Fig. 1. Serum bicarbonate before and after intravenous replacement with isotonic sodium chloride.

6 Isotonic sodium chloride in the early treatment of cholera diarrhea 67 Specific side effects reported [8] include paradoxical acidification of spinal fluid, increased carbon dioxide production which can aggravate acidemia by increasing arterial peal' and increase in lactic acid production. Additionally, it has been shown [11] that the acidosis in severe cholera is more profound than acidosis caused solely by loss of bicarbonate in the stool of patients, because of significant superimposed lactic acidemia and renal failure. Obviously, in poor countries without laboratory facilities available at even the hospital level, it is not possible to monitor the above-noted potentially undesirable effects of bicarbonate therapy. Our experience in Peru suggests that it might be possible to modify the standard timehonored international recommendation to use polyeiectrolitic solutions containing bicarbonate (or lactate) in the early treatment of hypovolemic shock secondary to cholera diarrhea. We think that it would be convenient to use isotonic sodium chloride in water for the early treatment of severe cholera diarrhea in underdeveloped countries. A large stock of this low-cost, easy-to-prepare solution should be continuously available in endemic cholera areas of the world, particularly in countries whose rates of severe illness due to cholera are higher than those reported for Peru [12]. We acknowledge that further larger prospective, adequately-designed clinical trials are needed to reach definitive conclusions about the role of exogenous bicarbonate in the initial intravenous fluid management of severely affected cholera patients. References 1. Situaci6n del c6lera. Boletin de la Oficina Sanitaria Panamericana May 1991; 110 (5), Situiaci6n del c6lera. Boletin de la Oficina Sanitaria Panamericana July 1991; 111 (1), Diarrhoeal Disease Control Programme. A Manualfor the Treatment ofdiarrhoea. For use by Physicians and other Senior Health Workers. Unpublished document WHOICDD/SER/80, Rev Pan American Health Organization. Cholera situation in the Americas. Epidemiol Bull 1991; 12, World Health Organization. Cholera. Weekly Epidemiol Rep 1992; 67, Baskett, J.F. Management of hypovolaemic shock. Br Med J 1990; 00, Watten, R.H., Morgan, F.M., Songkhla, Y.N., Vanikiata, B. and Philips, R.A. Water and electrolyte studies in cholera. J Clin Invest 1959; 8, Stacpoole, P.W. Lactic acidosis: the case against bicarbonate therapy (Editorial). Ann Intern Med 1986; 105, Narins, R.O. and Cohen, J.J. Bicarbonate therapy for organic acidosis: the case for its continued use. Ann Intern Med 1987; 106, Cooper, D.J., Walley, R.W., Wiggs, B.R. and Russell, J.A. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. Ann Intern Med 1990; 112, Wang, F., Butler, T., Rabbani, O.H. and Jones, P.K. The acidosis of cholera. N Engl J Med 1986; 15, World Health Organization. Cholera. Weekly Epidemiol Rep 1991; 66,