A Prospective Study of Pulmonary Function and Gas Exchange Following Liver Transplantation* Michael] Krowka, M.D., F.C.C.P.; E. Rolland Dickson, M.D.; Russell H. Wiesnet; M. D.; Ruud A. F. Krom, M. D.; Beth Atkinson, M. S.; and Denis A. Cortese, M.D., F.C.C.P.
Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0± 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three 6ndings were of clinical importance: PaC02 signi6cantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV/FVC, was
extremely uncommon posttransplant. Mean Dss improved signi6cantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation. (Chest 1992; 102:1161-66)
pulmonary dysfunction is associated with a variety of liver disorders.1.2 Orthotopic liver transplantation provides a unique opportunity to study changes in pulmonary function following improved hepatic function. Since the inception of the Mayo liver transplant program in 1985, we have prospectively studied pulmonary function and gas exchange parameters prior to and approximately one year following transplantation. This study reports the relationship between lung function and selected preoperative and postoperative variables which are clinically important in the management of liver transplant patients.
Predicted normal values for spirometry (FVC, FEV., FEF2.575%) were obtained from Knudson et al. ~ Predieted normal values for TLC were obtained from Miller. 3 Predicted RV ,,'as calculated from predicted TLC minus predicted FVC. Predieted MW was ealculated as 40 times the predicted FEV•. No inhaled bronchodilator a~ents were administered durin~ the assessment of expiratory airflow values. The Dss \\'as measured in each patient after PF assessment. The Dsb was measured in selected patients and predicted nornlal values were obtained from Miller et al. 5 The techniques in the steady state calculation previously have been published. A Briefl}~ each patient breathes room air for 1 min throu~h a three-way valve ,,·ith a nose dip in plaee to establish alveolar earbon monoxide baek pressure. The test ~as mixture of 0.1 percent earhon monoxide and air was breathed while the patient stepped up and down on a 9-inch step for approximately 3 min at a rate of 15 steps per minute. During the final minute of exercise, all expired gases were collected and the end-tidal carbon monoxide level was simultaneously measured. After eompletin~ the exercise, the patient continued to hreathe through the three-way valve, inspirin~ rooln air until the end-tidal carbon monoxide concentration reached a steady level, and this value was recorded as the back pressure fi)r carlx)n monoxide at the end of the test. The end-tidal sampling for carbon monoxide was done with a carbon monoxide analyzer (Mine Safety Institute, model 3(0) that was insensitive to both carbon dioxide and water vapor. Arterial blood gas levels were done \~/ith the suhjects hreathin~ room air in the sittin~ position at rest. Arterial-alveolar oxygen ~adients were ealculated using standard formulae. 3 Pretransplant clinical status in terms of severity of hepatie dysfunction was determined by using the Child's e1assification. -; This ineluded assessment of total bilirubin, serum albumin, elinieal aseites, nutrition and the existenee of encephalopathy. Child's C e1assification represented the most severe liver disease and Child's A elassification, minimal liver disease (Table I). The smoking status of each patient \\'as cate~orized into eurrent smokers, smokers who had quit and those who were never smokers. The smoking status was based upon data ohtained at the time of
METHODS
Complete PFT was obtained as part of routine pre- and post-liver transplant care in the outpatient laboratory. In every case, liver transplantation was eompleted within six months from the time of the PF assessment. Ei~ty-ei~ht pereent of patients were studied within three months of transplantation. The timin~ of posttransplant analysis was ehosen to be 9 to 15 months because this was the expeeted routine follow-up for all patients, as well a'i approximate time of onset of expiratory airflow problems if they develop. Pulmonary function testin~ included assessment ofTLC, R~ and ratio of RV to TLC by nitrogen washout. 3 Foreed vital eapacity, FEV., FEF25-75% and MW were measured with the use of a wed~e spirometer (Med Sei 560, Needham Heights, Mass). *From the Division of Thoraeic Diseases and Internal Medicine (Drs. Krowka and Cortese), Division of Gastroenterology and Internal Medieine (Drs. Dickson and \Viesner), Division of Transplantation Sur~ery (Dr. Krom), Section of Biostatistics (Ms. Atkinson), Mayo Clinic and Mayo Foundation, Rochester, Minn. Manuscript received August 12, 1991; revision accepted FebnIary 18. Reprint requests: Dr. Krotvka, Section of Thoracic Diseases, Mayo Clinic Jacksonville, 4.500 San Pablo Road, Jacksonville, FL 32224
=
= =
A.AT alpha.-antitrypsin de6ciency; CAH chronic active hepatitis; CRC cryptogenic cirrhosis; Deo diffusing capacity for carbon monoxide; Dsb = single-breath diffusing capacity for carbon monoxide; Dss steady state diffusing capacity for carbon monoxide; PBC primary biliary cirrhosis; PSC primary sclerosing cholangitis
=
=
=
CHEST I 102 I 4 I OCTOBER, 1992
=
1161
Table 1- Child's Classification for Severity of Liver Disease Class
Total Bilinlhin (mwdl)
Serum Albumin (Wdl)
Nutdtion
Ascites
Encephalopathy
A B C
3.5
>3.5 2.0-3.5
Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0± 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three 6ndings were of clinical importance: PaC02 signi6cantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV/FVC, was
extremely uncommon posttransplant. Mean Dss improved signi6cantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation. (Chest 1992; 102:1161-66)
pulmonary dysfunction is associated with a variety of liver disorders.1.2 Orthotopic liver transplantation provides a unique opportunity to study changes in pulmonary function following improved hepatic function. Since the inception of the Mayo liver transplant program in 1985, we have prospectively studied pulmonary function and gas exchange parameters prior to and approximately one year following transplantation. This study reports the relationship between lung function and selected preoperative and postoperative variables which are clinically important in the management of liver transplant patients.
Predicted normal values for spirometry (FVC, FEV., FEF2.575%) were obtained from Knudson et al. ~ Predieted normal values for TLC were obtained from Miller. 3 Predicted RV ,,'as calculated from predicted TLC minus predicted FVC. Predieted MW was ealculated as 40 times the predicted FEV•. No inhaled bronchodilator a~ents were administered durin~ the assessment of expiratory airflow values. The Dss \\'as measured in each patient after PF assessment. The Dsb was measured in selected patients and predicted nornlal values were obtained from Miller et al. 5 The techniques in the steady state calculation previously have been published. A Briefl}~ each patient breathes room air for 1 min throu~h a three-way valve ,,·ith a nose dip in plaee to establish alveolar earbon monoxide baek pressure. The test ~as mixture of 0.1 percent earhon monoxide and air was breathed while the patient stepped up and down on a 9-inch step for approximately 3 min at a rate of 15 steps per minute. During the final minute of exercise, all expired gases were collected and the end-tidal carbon monoxide level was simultaneously measured. After eompletin~ the exercise, the patient continued to hreathe through the three-way valve, inspirin~ rooln air until the end-tidal carbon monoxide concentration reached a steady level, and this value was recorded as the back pressure fi)r carlx)n monoxide at the end of the test. The end-tidal sampling for carbon monoxide was done with a carbon monoxide analyzer (Mine Safety Institute, model 3(0) that was insensitive to both carbon dioxide and water vapor. Arterial blood gas levels were done \~/ith the suhjects hreathin~ room air in the sittin~ position at rest. Arterial-alveolar oxygen ~adients were ealculated using standard formulae. 3 Pretransplant clinical status in terms of severity of hepatie dysfunction was determined by using the Child's e1assification. -; This ineluded assessment of total bilirubin, serum albumin, elinieal aseites, nutrition and the existenee of encephalopathy. Child's C e1assification represented the most severe liver disease and Child's A elassification, minimal liver disease (Table I). The smoking status of each patient \\'as cate~orized into eurrent smokers, smokers who had quit and those who were never smokers. The smoking status was based upon data ohtained at the time of
METHODS
Complete PFT was obtained as part of routine pre- and post-liver transplant care in the outpatient laboratory. In every case, liver transplantation was eompleted within six months from the time of the PF assessment. Ei~ty-ei~ht pereent of patients were studied within three months of transplantation. The timin~ of posttransplant analysis was ehosen to be 9 to 15 months because this was the expeeted routine follow-up for all patients, as well a'i approximate time of onset of expiratory airflow problems if they develop. Pulmonary function testin~ included assessment ofTLC, R~ and ratio of RV to TLC by nitrogen washout. 3 Foreed vital eapacity, FEV., FEF25-75% and MW were measured with the use of a wed~e spirometer (Med Sei 560, Needham Heights, Mass). *From the Division of Thoraeic Diseases and Internal Medicine (Drs. Krowka and Cortese), Division of Gastroenterology and Internal Medieine (Drs. Dickson and \Viesner), Division of Transplantation Sur~ery (Dr. Krom), Section of Biostatistics (Ms. Atkinson), Mayo Clinic and Mayo Foundation, Rochester, Minn. Manuscript received August 12, 1991; revision accepted FebnIary 18. Reprint requests: Dr. Krotvka, Section of Thoracic Diseases, Mayo Clinic Jacksonville, 4.500 San Pablo Road, Jacksonville, FL 32224
=
= =
A.AT alpha.-antitrypsin de6ciency; CAH chronic active hepatitis; CRC cryptogenic cirrhosis; Deo diffusing capacity for carbon monoxide; Dsb = single-breath diffusing capacity for carbon monoxide; Dss steady state diffusing capacity for carbon monoxide; PBC primary biliary cirrhosis; PSC primary sclerosing cholangitis
=
=
=
CHEST I 102 I 4 I OCTOBER, 1992
=
1161
Table 1- Child's Classification for Severity of Liver Disease Class
Total Bilinlhin (mwdl)
Serum Albumin (Wdl)
Nutdtion
Ascites
Encephalopathy
A B C
3.5
>3.5 2.0-3.5
