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Nitric oxide treatment of severe hypoxemia after liver transplantation in hepatopulmonary syndrome: Case report
Nitric Oxide Treatment of Severe Hypoxemia After Liver Transplantation in Hepatopulmonary Syndrome: Case Report John Alexander,* Anne Greenough,* Alastair Baker,* Mohamed Rela,† Nigel Heaton,† and Dennis Potter†
M
edical treatment of hepatopulmonary syndrome (HPS)1 has proved disappointing. The treatment of choice is orthotopic liver transplantation (OLT),2,3 but this is often complicated by intractable postoperative hypoxemia. Current evidence indicates that a successful outcome is possible in the presence of postoperative hypoxemia,4,5 but morbidity6 and mortality remains high.3,7 We report the successful use of inhaled nitric oxide in a child with HPS who developed severe hypoxemia after OLT.
Case Report A female child presented with hepatosplenomegaly and diarrhea; liver biopsy specimen showed micronodular cirrhosis. Cyanosis was noted when she was aged 3 years. A technetium 99m–labeled macroaggregated albumin scan showed a 46% shunt measured over the brain. Pulmonary angiography showed diffuse shunting at the bases indicated by early venous filling. Her pulmonary artery pressures were 29/12 mmHg, and pulmonary wedge pressure was 16 mmHg. Lung biopsy specimen did not show evidence of parenchymal disease. At 4 years she had an arterial oxygenation (PaO2) of 5.6 kPa and oxygen saturation (SaO2) of 78% to 81%. OLT was carried out. Over the subsequent 18 hours, PaO2 deteriorated despite a high inspired oxygen concentration (FIO2) and increase in the mean airway pressure (MAP). The oxygenation index (FIO2 3 100 3 MAP/PaO2) deteriorated from 15 to a maximum of 42. There was no evidence of consolidation on chest radiograph, and pulmonary artery pressures of 19/16 to 23/19 mmHg ruled out pulmonary hypertension. Her cardiac output index was 9.2–11.8 L/min/m2, and calculated systemic and pulmonary vascular resistance indices were 408–481 dyn-sec/cm5 and 47–68 dyn-sec/cm5, respectively. A noradrenaline infusion failed to increase calculated vascular resistance or oxygenation.
From the *Department of Child Health and the †Liver Transplant Surgical Service, King’s College Hospital, London, UK. Address reprint requests to Professor A. Greenough, Department of Child Health, King’s College Hospital, London SE5 9RS, UK. Copyright r 1997 by the American Association for the Study of Liver Diseases 1074-3022/97/0301-0008$3.00/0
54
In view of the continued deterioration, permission was requested and granted to carry out an inhaled nitric oxide (NO) trial. Continuous inhaled NO at 13 ppm was administered through a ventilator circuit port close to the endotracheal tube. This resulted in an immediate improvement in oxygen saturations and a fall in the oxygenation index (OI; Fig. 1). There was no change in pulmonary vascular resistance (51 dyn-sec/cm5), and cardiac output index was marginally lower at 7.4–7.9 L/min/m2. Changing the NO concentration did not lead to significant changes in oxygenation, but discontinuation resulted in a fall in oxygen saturation. Approximately 30 hours after NO inhalation was begun, there was a decrease in the oxygenation index; this was due to a reduction in the level of ventilatory support, which resulted in a reduction in MAP (Fig. 1) and, in retrospect, was inappropriate. The patient was ventilated for 9 days and extubated to face-mask continuous positive airways pressure with added NO at 1 ppm; this was discontinued 6 days later without any ill effects. The child subsequently made an unremarkable recovery. She was reviewed as an outpatient on day 42 after surgery and had an oxygen saturation of 95% in room air.
Discussion Hypoxemia in patients with liver failure and cirrhosis may have several causes.8-10 The deterioration in our patient was likely the result of an increase in intrapulmonary shunting and wor˙ ) missening of the ventilation-perfusion (V˙-Q match, because the pulmonary artery pressures were normal and there was evidence of peripheral vasodilatation with an increased cardiac ˙ mismatch output. Attempts to influence the V˙-Q by manipulating ventilator settings and using inotropes were unsuccessful, and this prompted NO use. As NO was administered by the inhaled route, we hoped to improve perfusion of the aerated parts of the lung without increasing the IPS. This resulted in an immediate improvement in oxygen˙ mismatch contribation. These results suggest V˙-Q utes to hypoxemia in HPS, at least after OLT, and inhaled NO in affected patients may improve oxygenation.
Liver Transplantation and Surgery, Vol 3, No 1 ( January), 1997: pp 54-55
Nitric Oxide and Hepatopulmonary Syndrome
55
Figure 1. Effect of inhaled nitric oxide (ppm) (N) on the OI (X) and oxygen saturation (S) after liver transplantation for the hepatopulmonary syndrome.
References 1. Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Intern Med 1995;122:521-529. 2. Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome—clinical observations and lack of therapeutic response to somatostatin analogue. Chest 1993; 104:515-521. 3. Hobeika J, Houssin D, Bernard O, Devictor D, Grimon G, Chapuis Y. Orthotopic liver transplantation in children with chronic liver disease and hypoxemia. Transplantation 1994;57:224-228. 4. van Obbergh L, Carlier M, De Clety SC, Sakal E, Rennotte MT, Veyckmans F, et al. Liver transplantation and pulmonary gas exchanges in hypoxemic children. Am Rev Respir Dis 1993;148:1408-1410. 5. McCloskey JJ, Schleien C, Schwarz K, Klein A, Colombani P. Severe hypoxemia and intrapulmonary shunting resulting from cirrhosis reversed by liver transplantation in a pediatric patient. J Pediatr 1991;118:902-904.
6. Schwarzenberg S, Freese DK, Regelmann WE, Gores PF, Boudreau RJ, Payne WD. Resolution of severe intrapulmonary shunting after liver transplantation. Chest 1993;103:1271-1273. 7. Mews CF, Dorney SF, Sheil AG, Forbes DA, Hill RE. Failure of liver transplantation in Wilson’s disease with pulmonary arteriovenous shunting. J Pediatr Gastroenterol Nutr 1990;10:230-233. 8. Moreau R, Lee SS, Soupison T, Roche-Sicot J, Sicot C. Abnormal tissue oxygenation in patients with cirrhosis and liver failure. J Hepatol 1988;7:98-105. 9. Moreau R, Lee SS, Hadengue A, Ozier Y, Sicot C, Lebrec D. Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: Effects of vasoactive drugs. Hepatology 1989;9:427-432. 10. Bihari D, Gimson AES, Waterson M, Williams R. Tissue hypoxia during fulminant hepatic failure. Crit Care Med 1985;13:1034-1039.
M
edical treatment of hepatopulmonary syndrome (HPS)1 has proved disappointing. The treatment of choice is orthotopic liver transplantation (OLT),2,3 but this is often complicated by intractable postoperative hypoxemia. Current evidence indicates that a successful outcome is possible in the presence of postoperative hypoxemia,4,5 but morbidity6 and mortality remains high.3,7 We report the successful use of inhaled nitric oxide in a child with HPS who developed severe hypoxemia after OLT.
Case Report A female child presented with hepatosplenomegaly and diarrhea; liver biopsy specimen showed micronodular cirrhosis. Cyanosis was noted when she was aged 3 years. A technetium 99m–labeled macroaggregated albumin scan showed a 46% shunt measured over the brain. Pulmonary angiography showed diffuse shunting at the bases indicated by early venous filling. Her pulmonary artery pressures were 29/12 mmHg, and pulmonary wedge pressure was 16 mmHg. Lung biopsy specimen did not show evidence of parenchymal disease. At 4 years she had an arterial oxygenation (PaO2) of 5.6 kPa and oxygen saturation (SaO2) of 78% to 81%. OLT was carried out. Over the subsequent 18 hours, PaO2 deteriorated despite a high inspired oxygen concentration (FIO2) and increase in the mean airway pressure (MAP). The oxygenation index (FIO2 3 100 3 MAP/PaO2) deteriorated from 15 to a maximum of 42. There was no evidence of consolidation on chest radiograph, and pulmonary artery pressures of 19/16 to 23/19 mmHg ruled out pulmonary hypertension. Her cardiac output index was 9.2–11.8 L/min/m2, and calculated systemic and pulmonary vascular resistance indices were 408–481 dyn-sec/cm5 and 47–68 dyn-sec/cm5, respectively. A noradrenaline infusion failed to increase calculated vascular resistance or oxygenation.
From the *Department of Child Health and the †Liver Transplant Surgical Service, King’s College Hospital, London, UK. Address reprint requests to Professor A. Greenough, Department of Child Health, King’s College Hospital, London SE5 9RS, UK. Copyright r 1997 by the American Association for the Study of Liver Diseases 1074-3022/97/0301-0008$3.00/0
54
In view of the continued deterioration, permission was requested and granted to carry out an inhaled nitric oxide (NO) trial. Continuous inhaled NO at 13 ppm was administered through a ventilator circuit port close to the endotracheal tube. This resulted in an immediate improvement in oxygen saturations and a fall in the oxygenation index (OI; Fig. 1). There was no change in pulmonary vascular resistance (51 dyn-sec/cm5), and cardiac output index was marginally lower at 7.4–7.9 L/min/m2. Changing the NO concentration did not lead to significant changes in oxygenation, but discontinuation resulted in a fall in oxygen saturation. Approximately 30 hours after NO inhalation was begun, there was a decrease in the oxygenation index; this was due to a reduction in the level of ventilatory support, which resulted in a reduction in MAP (Fig. 1) and, in retrospect, was inappropriate. The patient was ventilated for 9 days and extubated to face-mask continuous positive airways pressure with added NO at 1 ppm; this was discontinued 6 days later without any ill effects. The child subsequently made an unremarkable recovery. She was reviewed as an outpatient on day 42 after surgery and had an oxygen saturation of 95% in room air.
Discussion Hypoxemia in patients with liver failure and cirrhosis may have several causes.8-10 The deterioration in our patient was likely the result of an increase in intrapulmonary shunting and wor˙ ) missening of the ventilation-perfusion (V˙-Q match, because the pulmonary artery pressures were normal and there was evidence of peripheral vasodilatation with an increased cardiac ˙ mismatch output. Attempts to influence the V˙-Q by manipulating ventilator settings and using inotropes were unsuccessful, and this prompted NO use. As NO was administered by the inhaled route, we hoped to improve perfusion of the aerated parts of the lung without increasing the IPS. This resulted in an immediate improvement in oxygen˙ mismatch contribation. These results suggest V˙-Q utes to hypoxemia in HPS, at least after OLT, and inhaled NO in affected patients may improve oxygenation.
Liver Transplantation and Surgery, Vol 3, No 1 ( January), 1997: pp 54-55
Nitric Oxide and Hepatopulmonary Syndrome
55
Figure 1. Effect of inhaled nitric oxide (ppm) (N) on the OI (X) and oxygen saturation (S) after liver transplantation for the hepatopulmonary syndrome.
References 1. Lange PA, Stoller JK. The hepatopulmonary syndrome. Ann Intern Med 1995;122:521-529. 2. Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome—clinical observations and lack of therapeutic response to somatostatin analogue. Chest 1993; 104:515-521. 3. Hobeika J, Houssin D, Bernard O, Devictor D, Grimon G, Chapuis Y. Orthotopic liver transplantation in children with chronic liver disease and hypoxemia. Transplantation 1994;57:224-228. 4. van Obbergh L, Carlier M, De Clety SC, Sakal E, Rennotte MT, Veyckmans F, et al. Liver transplantation and pulmonary gas exchanges in hypoxemic children. Am Rev Respir Dis 1993;148:1408-1410. 5. McCloskey JJ, Schleien C, Schwarz K, Klein A, Colombani P. Severe hypoxemia and intrapulmonary shunting resulting from cirrhosis reversed by liver transplantation in a pediatric patient. J Pediatr 1991;118:902-904.
6. Schwarzenberg S, Freese DK, Regelmann WE, Gores PF, Boudreau RJ, Payne WD. Resolution of severe intrapulmonary shunting after liver transplantation. Chest 1993;103:1271-1273. 7. Mews CF, Dorney SF, Sheil AG, Forbes DA, Hill RE. Failure of liver transplantation in Wilson’s disease with pulmonary arteriovenous shunting. J Pediatr Gastroenterol Nutr 1990;10:230-233. 8. Moreau R, Lee SS, Soupison T, Roche-Sicot J, Sicot C. Abnormal tissue oxygenation in patients with cirrhosis and liver failure. J Hepatol 1988;7:98-105. 9. Moreau R, Lee SS, Hadengue A, Ozier Y, Sicot C, Lebrec D. Relationship between oxygen transport and oxygen uptake in patients with cirrhosis: Effects of vasoactive drugs. Hepatology 1989;9:427-432. 10. Bihari D, Gimson AES, Waterson M, Williams R. Tissue hypoxia during fulminant hepatic failure. Crit Care Med 1985;13:1034-1039.