Methods

Top Methods Results Discussion Author & Article Info References

Between July 1989 and June 1991, seven patients with confirmed HIV infection (six with AIDS; one with AIDS-related complex) [4] developed lactic acidosis. The patients presented with the following symptom complexes: nausea, emesis, and anorexia with weight loss (n = 4); fever and malaise (n = 2); and tachypnea with dyspnea (n = 3) (Table 1). Metabolic acidosis was diagnosed in three patients at admission to the hospital because of dyspnea, whereas dyspnea or a decrease in the blood bicarbonate level led to evaluation of arterial blood gases in four other patients (Table 1). The control group included nine age-matched patients admitted to the same intensive care unit over the same interval who had placement of a pulmonary artery catheter [5] for close monitoring of volume status. When studied, all controls were normovolemic (normal cardiac output and pulmonary artery pressure), and none had metabolic acidosis, hypoxia, or clinical evidence of a mixed acid-base disorder. The cardiac output was determined by thermodilution [5]; the blood lactate level, oxygen delivery, and oxygen utilization were assessed as previously reported [6, 7]. Data are expressed as mean ±SD. The unpaired Student t-test was used for comparisons.

Results

Top Methods Results Discussion Author & Article Info References

When lactic acidosis was diagnosed, six of the seven patients were lucid and generally had no symptoms except hyperventilation (see Table 1). Other causes for elevated anion gap metabolic acidosis, such as diabetic ketoacidosis, malignancy, sepsis, uremia, thyrotoxicosis, or exogenous intoxication were ruled out by appropriate laboratory tests and diagnostic procedures and by autopsy in four cases. No single drug was being taken by all seven patients: Four patients were receiving zidovudine, one patient was receiving ganciclovir, and one patient was receiving clofazimine. Values at the time of diagnosis of lactic acidosis (see Table 1) were as follows: arterial oxygen saturation, 98% ± 1%; arterial lactate, 14.3 ± 2.6 mmol/L (controls, 1.6 ± 0.8 mmol/L; P < 0.001); and anion gap, 28 ± 5 mmol/L (controls, 11 ± 2 mmol/L; P < 0.001). The oxygen extraction ratio {100 x (arterial O₂ – venous O₂)/arterial O₂} (O₂ expressed as mL O_2/100 mL blood) was 24.9% ± 6.0%, which did not differ from that of controls (19.5% ± 7.8%; P = 0.2).

In three patients, the cardiac index was 3.20 ± 0.21 L/min per m (²) body surface area (control value 3.19 ± 1.38 L/min per m²; P > 0.2) when the blood lactate level was 14.2 mmol/L. The systemic oxygen delivery was 938 ± 118 mL/min (controls, 1137 ± 490 mL/min; P > 0.2) and oxygen utilization was 211 ± 51 mL/min (controls, 213 ± 87 mL/min; P > 0.2). Thus, cardiac output, oxygen extraction, and both oxygen delivery and utilization were in the normal range [7, 8] and did not differ in controls (Figure 1).

View larger version (21K): [in this window] [in a new window]   Figure 1. Oxygen delivery, oxygen utilization, and cardiac index in three patients with the acquired immunodeficiency syndrome (AIDS) and lactic acidosis and in nine control patients. The cardiac index and oxygen delivery and utilization are all within one standard deviation (SD) of the control values. Data are presented as mean ±SD.

Four patients died of cardiovascular collapse secondary to progressive metabolic acidosis (see Table 1). In all four, the arterial pH fell below 6.85 and the lactate level was higher than 15 mmol/L before death. However, in the other three patients, arterial pH and blood levels of lactate did not change substantially during hospitalization, and all were discharged in a lucid and ambulatory state. Within 15 months, all had died of other complications of AIDS (see Table 1).

Discussion

Top Methods Results Discussion Author & Article Info References

In seven patients with HIV infection who did not have shock, sepsis, malignancy, or other causes of systemic hypoxemia, lactic acidosis developed suddenly and without obvious cause. In these patients, the arterial P_o2, cardiac index, oxygen delivery, oxygen utilization, and oxygen extraction ratio were not significantly different from those of controls, providing no evidence for systemic hypoxemia or tissue hypoxia. Although oxygen delivery and utilization were evaluated in only three patients, the normal oxygen extraction ratio strongly suggests that all had normal oxygen utilization. All had normal blood pressure with no evidence of shock or sepsis, so that substantial shunting of blood was clinically unlikely.

The disorder in the patients resembled adult Reye syndrome, in that type B lactic acidosis was associated with a probable infectious cause [9]. Increased production of lactate may also have been associated with a myopathy related to zidovudine therapy. Such a myopathy can cause a decrease of muscle respiratory chain capacity in some patients with AIDS [10]. Lactic acidosis was a major comorbid event in four patients, but the other three survived an average of 32 weeks, suggesting a heterogeneous cause.

This study was presented in part at the 23rd Annual Meeting, American Society of Nephrology, November 1991, Baltimore, Maryland.