Case Report

Acute Hypercapnic Respiratory Failure Associated With Hemodialysis

Carlos R. Franco Palacios, MD; Abdullah Altayeh, MD; Qi Qian, MD Drs. Palacios and Qian are with the Department of Medicine, Division of Nephrology and Hypertension, and Dr. Altayeh is with the Department of Critical Care Medicine, Mayo Clinic, College of Medicine, Rochester, Minnesota.

Patients undergoing hemodialysis are subject to recurrent acid-base perturbations. Prior to each dialysis treatment, they are relatively acidemic, which is corrected rapidly during dialysis. We report a patient with obesity, obstructive lung disease, and pneumonia who developed acute respiratory failure triggered by an inux of high bicarbonate during dialysis. This case emphasizes that in patients with severely compromised respiratory reserve, a large amount of bicarbonate inux during hemodialysis may cause acute CO2 accumulation and ventilatory distress. An individualized approach with judicious adjustment of the dialysate bicarbonate concentration may be necessary.

atients undergoing chronic hemodialysis are regularly subject to acute shifts in extracellular acidbase balance. In the interval between dialysis treatments, they accumulate non-volatile acidic metabolites and become progressively acidemic. These acids are acutely neutralized and cleaned off at each dialysis session. Routinely used superphysiological bicarbonate concentration (37 meq/L HCO3) in dialysate corrects the acidosis and creates an initial mild metabolic alkalosis at the end of each dialysis. Such acid-base changes are rapid with modern-day high-ux dialyzers. In patients with adequate pulmonary reserve, the dialysis-associated acid-base shift is overcome primarily via respiratory compensation. In general, blood pH (with compensation) at the end of each dialysis is kept at near physiological range. However, in patients with severe underlying pulmonary structural and functional abnormalities, routinely employed dialysis prescription may not be tolerated and can be potentially detrimental. We present a case of acute respiratory failure temporally associated with hemodialysis initiation, consistent with acute hypercapnia triggered by rapid bicarbonate inux from dialysis. This case underscores the importance of individualizing dialysis prescriptions for patients
DOI: 10.1002/dat.20506

with compromised pulmonary ventilatory reserve.

Case Report
A 55-year-old man with kidney failure due to diabetes and hypertension, on intermittent hemodialysis thrice weekly for the prior 5 years, was admitted for acute pneumococcal pneumonia. He had multiple medical comorbidities including morbid obesity (weight: 136 kg, body mass index: 44), chronic obstructive pulmonary disease (COPD) with hypercapnia (baseline arterial blood gas on room air: pH 7.37, PCO2 48 mmHG, PO2 84 mmHG [on a non-dialysis day] and pre-dialysis blood HCO3: 2429 mEq/L), and heart failure (ejection fraction: 44%). He required mechanical ventilation, and infection was effectively controlled with antibiotics. By hospital day 5, he was weaned off ventilation and resumed oral intake (from NG tube feeds). He had been maintained on his regular dialysis schedule and prescription of 37 mEq/L dialysate bicarbonate since admission. At his rst dialysis post extubation (hospital day 7), he was noted to be exceedingly drowsy, but awakable, and his digital O2 saturations were stable ( 90%). On his subsequent dialysis (hospital day 9), he developed acute hypop-

nea and hypoxia (O2 saturation 50%) at ~15-20 minutes after being connected to the dialyzer. The dialysis was promptly discontinued, and oxygen provided. However, he remained hypopneic and became unresponsive, requiring resuscitation and intubation. His arterial blood gas during resuscitation (~10 minutes after the discontinuation of the dialysis) was pH 7.22, PCO2 78 mmHg, PO2 66 mmHg, and calculated HCO3 32 mEq/L. The patient was transferred to the medical intensive care unit (ICU). On examination in the ICU, he was responsive, with a pulse of 92/min, respiratory rate 18/min, O2 saturation 96% on mechanical ventilation (assist control, rate of 14, low tidal volume of 500 mL to prevent lung injury, PEEP of 5 and FIO2 of 40%), blood pressure 112/52 mmHg, and temperature 37.5C. His breath sounds were reduced, and scattered crackles were noted at bilateral lung bases. His heart rate was regular, without murmurs or rubs, abdomen obese and non-tender, and extremities without edema. His chest x-ray showed cardiomegaly, pulmonary inltrates, and vascular congestion, which was not signicantly different from the x-ray on the prior day. Laboratory study results after ICU arrival were as follows: WBC count 8.5 109/L, hemoglobin 9.2 g/dL, sodium 130 mEq/L, potassium 5.1 mEq/L,
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Case Report

bicarbonate 28 mEq/L, and creatinine 4.5 mg/dL. His ventilatory status was stabilized, and 4 hours later he was transitioned to bi-level positive airway pressure ventilation (BIPAP). About 8 hours later, his ABG was pH 7.32, PCO2 60 mmHg, PO2 75 mmHg, and serum bicarbonate 30 mEq/L. Based on his previous pre-dialysis blood bicarbonate, we provided hemodialysis for him with a reduced dialysate bicarbonate concentration, 28 mEq/L for his rst ICU dialysis run and 30 mEq/L for the second run on the following day. He tolerated both runs without any adverse respiratory event. He was weaned off BIPAP after the second dialysis and transferred back to the regular medical unit. During his subsequent hemodialysis, the dialysate bicarbonate concentration was adjusted to between 27 and 30 mEq/L according to his status. He was discharged 2 weeks later. His in-patient dialysis history was conveyed to his out-patient dialysis unit.

Discussion
Acute bicarbonate inux during dialysis, although traditionally considered a benign condition, can potentially be detrimental. In our patient, the tight temporal association of the dialysis initiation and onset of acute hypercapnic respiratory failure, and the subsequent tolerability of dialysis with a reduced bicarbonate concentration, indicate that the abrupt bicarbonate inux during dialysis was the initial trigger of his respiratory decompensation. Pre-dialysis metabolic acidosis is a prominent feature in dialysis patients. An anuric, non-hypercatabolic dialysis patient retains ~70-80 mEq of H+ daily. The anion gap is typically elevated in this setting as the retained anions (phosphate, sulfate, urate, and hippurate) are non-volatile. Adverse sequelae from sustained metabolic acidosis are multiple, including negative nitrogen balance, protein wasting, anorexia, fatigue, bone loss, depression of cardiac contractility, arrhythmias, gastrointestinal disturbances, hormonal derangements, insulin resistance, hyperkalemia, altered gluconeogenesis and triglyceride metabolism, and (in children) growth retardation.1
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Hemodialysis corrects acidosis and mitigates the academia-associated detrimental effects. However, abrupt bicarbonate inux through this mechanism can trigger several adverse effects. First, an acute raise in blood pH can cause hypoventilation and respiratory depression. This effect is well known and is mediated via both central and peripheral chemoreceptors.2 Second, alkalosis depresses tissue oxygen delivery by inducing vasoconstriction and by shifting the oxygen dissociation curve to the left, thereby impairing hemoglobins ability to release oxygen.3 Alkalosis-induced tissue hypoxemia can thus adversely affect vital organs, including cerebral, cardiovascular, and pulmonary functions. Third, abrupt reduction in the circulating H+ concentration (neutralized by bicarbonate inux) acutely reduces the circulating ionized pool of calcium, leading to functional hypocalcemia and ensuing neuromuscular/end-organ functional impairment, including diaphragmatic muscle weakness. Although bicarbonate administrationrelated disadvantages are well known, they have not been the focus of our daily practice because bicarbonate provided through routine dialysis has not been shown to be overtly consequential. Two factors are likely attributable to such a

subclinical presentation: 1) the bicarbonate load with dialysis, although high, is not extremely excessive; and 2) the bodys compensatory mechanisms, including CO2 exhalation (which was compromised in our patient), are able to buffer the acute bicarbonate-mediated effects. Thus, bicarbonate inux via dialysis is generally well tolerated, although cases of extremely high alkali/bicarbonate administration above and beyond the capacity of compensatory mechanisms have been reported and are associated with serious clinical consequences.4,5 In our patient, the initial bicarbonate-loading triggered adverse effects were augmented by his severely compromised reserve (morbid obesity, underlying COPD, congestion, and recent pneumonia). The arterial blood gas obtained during resuscitation already showed that he had developed CO2 retention and respiratory acidosis. Nonetheless, his calculated bicarbonate concentration at that time was still high, consistent with high bicarbonate inux from dialysis. If the blood gas were obtained before the onset of respiratory failure, he would most certainly have been alkalemic. As shown in Figure 1A, his baseline COPD/chronic CO2 retention and the recent lung parenchymal injury (pneumonia) rendered him

FIGURE 1. Proposed pathogenesis of the patients acute respiratory failure. A, The sequelae of abrupt bicarbonate infusion at dialysis. B, The genesis of acute CO2 accumulation. COPD, chronic obstructive pulmonary disease.

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highly sensitive to the respiratory-depressive effects of exogenous bicarbonate. His diaphragmatic excursion was diminished at baseline due to his COPD (hyperination of lung parenchyma) and morbid obesity; the acute reduction in the ionized pool of circulating calcium would further weaken the diaphragmatic muscle strength, lowering the ventilatory force. Additionally, respiratory muscle fatigue from attempting to excrete the excess CO2 load likely would have contributed to his decompensation. Moreover, because of his chronic lung disease and sustained respiratory acidosis, his hemoglobin O2 dissociation curve likely chronically shifted to the right. The acute bicarbonate inux would shift the O2 dissociation curve to the left, reducing tissue O2 delivery, which likely contributed to his acute loss of mental lucidity. Taken together, the disadvantages of dialysis-associated bicarbonate inux were amplied in this case and likely played a key role in the genesis of his respiratory failure. This case cautions us to be vigilant and to individualize dialysis prescriptions for kidney failure patients with severe pulmonary dysfunction. In patients with severe compound lung-kidney dysfunction,

the combined effect of chronic respiratory acidosis and insufcient metabolic compensatory response (defect in kidney bicarbonate regeneration) creates a clinical management conundrum. On the one hand, insufcient kidney-mediated metabolic compensation in hypercapnic patients can increase mortality,6 making bicarbonate repletion (via dialysis) critically important. On the other hand, over or rapid bicarbonate loading can induce metabolic alkalosis (an acid-base alteration shown to increase mortality in several hospital settings7-9), which may trigger worsening CO2 retention, ushering in acute respiratory acidosis, another potentially lethal condition. As illustrated in our case, correction of acid-base alterations during hemodialysis may not be straightforward. The dialysate bicarbonate concentration unt for individual patients can be potentially detrimental. In summary, caution should be exercised when providing dialysis for patients with severe pulmonary dysfunction, obesity, and other comorbidities. An individualized approach is necessary under special circumstances; judicious adjustment of dialysate bicarbonate concentration can

prevent acute respiratory failure and be lifesaving. D&T

References
1. Mitch WE. Metabolic and clinical consequences of metabolic acidosis. J Nephrol. 2006;19(suppl 9):S70-75. 2. Javaheri S, Shore NS, Rose B, et al. Compensatory hypoventilation in metabolic alkalosis. Chest. 1982;81:296-301. 3. Riggs AF. The Bohr effect. Annu Rev Physiol. 1988;50:181-204. 4. Diskin CJ, Stokes TJ, Dansby LM, et al. Recurrent metabolic alkalosis and elevated troponins after crack cocaine use in a hemodialysis patient. Clin Exp Nephrol. 2006;10:156-158. 5. Nagai Y, Itabashi M, Mizutani M, et al. A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura. Ther Apher Dial. 2008;12:86-90. 6. Ucgun I, Oztuna F, Dagli CE, et al. Relationship of metabolic alkalosis, azotemia and morbidity in patients with chronic obstructive pulmonary disease and hypercapnia. Respiration. 2008;76:270274. 7. Galla JH. Metabolic alkalosis. J Am Soc Nephrol. 2000;11:369-375. 8. Webster NR, Kulkarni V. Metabolic alkalosis in the critically ill. Crit Rev Clin Lab Sci. 1999;36:497510. 9. Tovbin D, Heimer D, Mashal A, et al. Intradialytic hypercapnic respiratory failure managed by noninvasive assisted ventilation. Am J Nephrol. 2001;21:383-385.

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