- Email: [email protected]
Severe Metabolic Alkalosis Complicating Regional Citrate Hemodialysis
Severe Metabolic Alkalosis Complicating Regional Citrate Hemodialysis Stephen P. Kelleher, MD, and Gerald Schulman, MD • Regional citrate hemodialysis has been effectively used as an alternative to heparin anticoagulation during dialysis of patients at increased risk for bleeding. Few complications have been noted; however, we report the occurrence of severe metabolic alkalosis in two patients requiring high infusion rates of citrate during hemodialysis while being mechanically ventilated. Careful monitoring of acid-base status is mandatory in this seHing, and reduction of citrate dose may be advisable. © 1987 by the National Kidney Foundation, Inc. INDEX WORDS: Citrate-hemodialysis-metabolic alkalosis.
R
EGIONAL citrate hemodialysis (RD) has been effectively used as an alternative to heparin anticoagulation during dialysis of patients at high risk for bleeding.)·2 Dialyzer efficiency is comparable to that obtained during standard heparinization, and few complications have been noted. In a series of 15 citrate dialyses, Pinnick et all reported no acid-base disorders. However, in the present paper, we describe two patients in whom severe metabolic alkalosis developed as an apparent complication of citrate RD. CASE REPORTS
Case 1 MB was a 72-year-old man with chronic renal failure of unknown etiology. Abrupt deterioration of neurologic function led to the diagnosis of subdural hematoma, which was surgically evacuated. The postoperative course was complicated by sepsis and worsening azotemia eventually necessitating dialysis. Liver function tests were within normal limits. To minimize risk of intracranial hemorrhage, HD using regional citrate anticoagulation, according to the protocol of Pinnick et aI, I was employed. Over a 48-hour period, two four-hour dialyses were performed using a CF-1211 0.8-m' hollow fiber dialyzer (Travenol, Inc, Deerfield, IL) and calcium-free acetate (37 mEq/L) dialysate. Blood flow rate was 200 mUmin, and citrate was infused at a rate sufficient to achieve a dialyzer-activated clotting time of 125 seconds, 1.5 times baseline. The calculated final concentration of citrate in blood entering the dialyzer was 6.5 mmol/L, within recommended limits. The patient underwent mechanical ventilation during the entire period. Effective dialysis was accomplished; however, as noted in Table I, severe metabolic alkalosis developed in the absence of other known causes. Subsequently, the patient was converted to low-dose heparinization during dialysis with resolution of the metabolic alkalosis.
Case 2 RC was a 68-year-old man who underwent cholecystectomy following acute cholecystitis. Postoperatively, the patient suffered a myocardial infarction and hypotension that led to acute tubular necrosis. The patient required mechanical ventilation
and had episodes of upper gastrointestinal hemorrhage secondary to stress ulceration. Liver function tests were within normal limits. Because of progressive azotemia , HD was initiated. Due to recent surgery and gastrointestinal bleeding, citrate regional anticoagulation was employed during the HD treatment with a CDAK 1.3-m' hollow fiber dialyzer (Cordis-Dow, Inc , Miami) . In an attempt to maintain the activated clotting time at 1.5 times baseline, sodium citrate was infused at a rate sufficient to raise the calculated citrate concentration in the blood entering the dialyzer to 7.2 mmol/ L at a blood flow rate of 200 mLlmin. Although the clotting time was 90 seconds and did not reach the desired goal, the treatment was successfully completed without clotting of the dialyzer. An arterial blood gas measurement 90 minutes after the procedure demonstrated severe metabolic alkalosis (Table 1). The patient was undergoing nasogastric suction at the time; however, gastric pH while the patient was receiving cimetidine was consistently greater than 4. Subsequent heparin dialyses ameliorated the alkalosis despite continued nasogastric suction .
DISCUSSION
Metabolic alkalosis due to administration of parenteral alkali, especially in the setting of renal failure, has previously been reported as a complication of bicarbonate or lactate infusion, administration of plasma protein fractions that are very rich in sodium acetate, 3 and massive transfusion of blood that has been stored in citrate. 4 In the present paper, we report two cases of severe metabolic alkalosis that developed during regional citrate HD in the absence of other known causes . The patient in case 2 was undergoing nasogastric suction, but it should be noted that alkalosis develFrom the Departments of Nephrology and Medicine, State University of New York at Stony Brook; and Northport I1!terans Administration Hospital, NY Address reprint requests to Stephen P. Kelleher, MD, Division of Nephrology, HSC TlS-020, SUNY at Stony Brook, Stony Brook, NY 11794. © 1987 by the National Kidney Foundation , Inc. 0272-638618710903-0009$03.0010
American Journal of Kidney Diseases, Vol IX, No 3 (March), 1987: pp 235-236
235
236
KELLEHER AND SCHULMAN Table 1. Arterial Blood Gases Before and After Citrate Dialysis HC0 3
Patient 1 Before After Patient 2 Before After
PC0 2
pH
(mEq/L)
(mm Hg)
7.41 7.56
26 38
38 38
7.35 7.58
22 37
39 41
oped abruptly during citrate dialysis, that gastric pH was greater than 4 due to the use of cimetidine, and that the alkalosis resolved during heparin dialysis despite continued nasogastric suction. Previous reports have not described alkalosis as a complication of citrate dialysis. I .2 We believe that metabolic alkalosis was prominent in our cases for several reasons. First, the dose of citrate required to achieve desired anticoagulation, while still within recommended guidelines, was relatively large and was calculated to achieve final concentrations of 6.5 mmol/L and 7.2 mmollL in blood entering the dialyzer. Dialyzer clearance of citrate has been reported to be 60% of urea clear-
ance,5 and therefore it seems probable that significant amounts of citrate may have entered the patients' circulation; each milliequivalent of citrate represents a potential milliequivalent of bicarbonate. Second, dialysis on consecutive days in case 1 may have greatly augmented delivery of potential bicarbonate to the ·patient. Third, the setting of mechanical ventilation prevented normal respiratory compensation and thus allowed maximum expression of the metabolis alkalosis. It seems likely that these factors combined to produce a clinically important metabolic derangement. In summary, severe metabolic alkalosis developed in two patients receiving high doses of citrate anticoagulation for HD while undergoing mechanical ventilation. Since the optimum method for assessing the adequacy of citrate anticoagulation has not yet been determined ,6 our practice is to avoid high infusion rates of citrate in settings similar to the present report. We have not observed dialyzer clotting when citrate is infused at rates calculated to achieve a concentration of 2.5 to 5.0 mmollL in the blood entering the dialyzer, even when the activated clotting time is not increased to 1.5 times the baseline value.
REFERENCES I. Pinnick RV, Wiegmann TB, Diederich DA: Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 308:258-261 , 1983 2. Seaton RD. Duncan KA , Pinnick RV, et al: Regional citrate anticoagulation in chronic hemodialysis patients. Trans Am Soc Artif Intern Organs 29:414-417, 1983 3. Wilson RF, Gibson D, Percinal AK, et al: Severe alkalosis in critically ill surgical patients. Arch Surg 105: 197-202, 1972 4. Rahilly GT, Berl T: Severe metabolic alkalosis caused by
administration of plasma protein fraction in end stage renal failure. N Engl J Med 301:824-826, 1979 5. Winchester JF, Gelfand Me , Krepshield JH , et al: Dialysis and hemoperfusion of poisons and drugs-Update. Trans Am Soc Artif Intern Organs 23:762-842, 1977 6. Schwartz EN, Turner G, Hunt W, et al: Regional citrate anticoagulation for hemodialysis: Report of six hundred treatments. Proceedings of the XVII Annual Meeting of the American Society of Nephrologists, 1984 (abstr 55)
R
EGIONAL citrate hemodialysis (RD) has been effectively used as an alternative to heparin anticoagulation during dialysis of patients at high risk for bleeding.)·2 Dialyzer efficiency is comparable to that obtained during standard heparinization, and few complications have been noted. In a series of 15 citrate dialyses, Pinnick et all reported no acid-base disorders. However, in the present paper, we describe two patients in whom severe metabolic alkalosis developed as an apparent complication of citrate RD. CASE REPORTS
Case 1 MB was a 72-year-old man with chronic renal failure of unknown etiology. Abrupt deterioration of neurologic function led to the diagnosis of subdural hematoma, which was surgically evacuated. The postoperative course was complicated by sepsis and worsening azotemia eventually necessitating dialysis. Liver function tests were within normal limits. To minimize risk of intracranial hemorrhage, HD using regional citrate anticoagulation, according to the protocol of Pinnick et aI, I was employed. Over a 48-hour period, two four-hour dialyses were performed using a CF-1211 0.8-m' hollow fiber dialyzer (Travenol, Inc, Deerfield, IL) and calcium-free acetate (37 mEq/L) dialysate. Blood flow rate was 200 mUmin, and citrate was infused at a rate sufficient to achieve a dialyzer-activated clotting time of 125 seconds, 1.5 times baseline. The calculated final concentration of citrate in blood entering the dialyzer was 6.5 mmol/L, within recommended limits. The patient underwent mechanical ventilation during the entire period. Effective dialysis was accomplished; however, as noted in Table I, severe metabolic alkalosis developed in the absence of other known causes. Subsequently, the patient was converted to low-dose heparinization during dialysis with resolution of the metabolic alkalosis.
Case 2 RC was a 68-year-old man who underwent cholecystectomy following acute cholecystitis. Postoperatively, the patient suffered a myocardial infarction and hypotension that led to acute tubular necrosis. The patient required mechanical ventilation
and had episodes of upper gastrointestinal hemorrhage secondary to stress ulceration. Liver function tests were within normal limits. Because of progressive azotemia , HD was initiated. Due to recent surgery and gastrointestinal bleeding, citrate regional anticoagulation was employed during the HD treatment with a CDAK 1.3-m' hollow fiber dialyzer (Cordis-Dow, Inc , Miami) . In an attempt to maintain the activated clotting time at 1.5 times baseline, sodium citrate was infused at a rate sufficient to raise the calculated citrate concentration in the blood entering the dialyzer to 7.2 mmol/ L at a blood flow rate of 200 mLlmin. Although the clotting time was 90 seconds and did not reach the desired goal, the treatment was successfully completed without clotting of the dialyzer. An arterial blood gas measurement 90 minutes after the procedure demonstrated severe metabolic alkalosis (Table 1). The patient was undergoing nasogastric suction at the time; however, gastric pH while the patient was receiving cimetidine was consistently greater than 4. Subsequent heparin dialyses ameliorated the alkalosis despite continued nasogastric suction .
DISCUSSION
Metabolic alkalosis due to administration of parenteral alkali, especially in the setting of renal failure, has previously been reported as a complication of bicarbonate or lactate infusion, administration of plasma protein fractions that are very rich in sodium acetate, 3 and massive transfusion of blood that has been stored in citrate. 4 In the present paper, we report two cases of severe metabolic alkalosis that developed during regional citrate HD in the absence of other known causes . The patient in case 2 was undergoing nasogastric suction, but it should be noted that alkalosis develFrom the Departments of Nephrology and Medicine, State University of New York at Stony Brook; and Northport I1!terans Administration Hospital, NY Address reprint requests to Stephen P. Kelleher, MD, Division of Nephrology, HSC TlS-020, SUNY at Stony Brook, Stony Brook, NY 11794. © 1987 by the National Kidney Foundation , Inc. 0272-638618710903-0009$03.0010
American Journal of Kidney Diseases, Vol IX, No 3 (March), 1987: pp 235-236
235
236
KELLEHER AND SCHULMAN Table 1. Arterial Blood Gases Before and After Citrate Dialysis HC0 3
Patient 1 Before After Patient 2 Before After
PC0 2
pH
(mEq/L)
(mm Hg)
7.41 7.56
26 38
38 38
7.35 7.58
22 37
39 41
oped abruptly during citrate dialysis, that gastric pH was greater than 4 due to the use of cimetidine, and that the alkalosis resolved during heparin dialysis despite continued nasogastric suction. Previous reports have not described alkalosis as a complication of citrate dialysis. I .2 We believe that metabolic alkalosis was prominent in our cases for several reasons. First, the dose of citrate required to achieve desired anticoagulation, while still within recommended guidelines, was relatively large and was calculated to achieve final concentrations of 6.5 mmol/L and 7.2 mmollL in blood entering the dialyzer. Dialyzer clearance of citrate has been reported to be 60% of urea clear-
ance,5 and therefore it seems probable that significant amounts of citrate may have entered the patients' circulation; each milliequivalent of citrate represents a potential milliequivalent of bicarbonate. Second, dialysis on consecutive days in case 1 may have greatly augmented delivery of potential bicarbonate to the ·patient. Third, the setting of mechanical ventilation prevented normal respiratory compensation and thus allowed maximum expression of the metabolis alkalosis. It seems likely that these factors combined to produce a clinically important metabolic derangement. In summary, severe metabolic alkalosis developed in two patients receiving high doses of citrate anticoagulation for HD while undergoing mechanical ventilation. Since the optimum method for assessing the adequacy of citrate anticoagulation has not yet been determined ,6 our practice is to avoid high infusion rates of citrate in settings similar to the present report. We have not observed dialyzer clotting when citrate is infused at rates calculated to achieve a concentration of 2.5 to 5.0 mmollL in the blood entering the dialyzer, even when the activated clotting time is not increased to 1.5 times the baseline value.
REFERENCES I. Pinnick RV, Wiegmann TB, Diederich DA: Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 308:258-261 , 1983 2. Seaton RD. Duncan KA , Pinnick RV, et al: Regional citrate anticoagulation in chronic hemodialysis patients. Trans Am Soc Artif Intern Organs 29:414-417, 1983 3. Wilson RF, Gibson D, Percinal AK, et al: Severe alkalosis in critically ill surgical patients. Arch Surg 105: 197-202, 1972 4. Rahilly GT, Berl T: Severe metabolic alkalosis caused by
administration of plasma protein fraction in end stage renal failure. N Engl J Med 301:824-826, 1979 5. Winchester JF, Gelfand Me , Krepshield JH , et al: Dialysis and hemoperfusion of poisons and drugs-Update. Trans Am Soc Artif Intern Organs 23:762-842, 1977 6. Schwartz EN, Turner G, Hunt W, et al: Regional citrate anticoagulation for hemodialysis: Report of six hundred treatments. Proceedings of the XVII Annual Meeting of the American Society of Nephrologists, 1984 (abstr 55)