Anesth Analg

The efficacy and safety of a clonidine/bupivacaine combination in caudal blockade for pediatric hernia repair.

Klimscha W. Chiari A. Michalek-Sauberer A. Wildling E. Lerche A. Lorber C. Brinkmann H. Semsroth M.
Department of Anesthesiology and Intensive Care, University of Vienna, Austria. walter.klimscha@univie.ac.at
We evaluated the analgesic efficacy and hemodynamic and respiratory safety of clonidine when added to bupivacaine for caudal blocks in 58 children aged 38 +/- 2 mo (mean +/- SEM). Patients scheduled for ambulatory hernia repair were randomly given a caudal injection (0.75 mL/kg) of either saline placebo (P group), bupivacaine, 0.25% (B group), bupivacaine plus epinephrine 1:200,000 (BE group), bupivacaine plus clonidine 1 microgram/kg (BC1 group), or bupivacaine plus clonidine 2 micrograms/kg (BC2 group). Postoperative measurements included duration of analgesia, hemodynamics, and respiratory monitoring for 6 h. Thereafter, parents assessed their child's analgesic requirements at home every 3 h for 18 h. The duration of analgesia (median [range]) was significantly longer (P < 0.05) in the BC1 and BC2 groups (360 [270-360] min and 360 [355-360] min, respectively) compared with the P (77[45-190]), B (346[105-360]), or BE group (300[75-360]). Similarly, the BC1 and BC2 groups required less additional analgesic within the first 24 h. All groups showed a significant decrease in mean arterial pressure compared with baseline values, but the differences among the groups were not significant. Bradycardia and respiratory depression were not observed. Clonidine 1 and 2 micrograms/kg can be safely added to bupivacaine caudal blockade in small children for ambulatory hernia repair to achieve an increased duration of analgesia compared with bupivacaine alone or bupivacaine plus epinephrine. Implications: The addition of clonidine, an antihypertensive drug with analgesic properties, to local anesthetics in caudal blocks prolongs postoperative pain relief and reduces the need for additional pain treatment in children after hernia operation.

Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy.

Groudine SB. Fisher HA. Kaufman RP Jr. Patel MK. Wilkins LJ. Mehta SA. Lumb PD.
Department of Anesthesiology, Albany Medical College, New York 12208, USA. ScottvGroudine@ccgateway.amc.edu
Postoperative ileus is a concern among surgical patients. Epidural anesthesia and analgesia with local anesthetics can decrease the duration of ileus. Significant systemic absorption of local anesthesia occurs during epidural use. In this study, we examined whether many of the beneficial effects on bowel function seen with epidural lidocaine are also present when the drug is given parenterally. Forty patients undergoing radical retropubic prostatectomy were studied with one half of the patients receiving a lidocaine bolus (1.5 mg/kg) and infusion (3 mg/min, unless weight

The hemodynamic effects of pneumoperitoneum during laparoscopic surgery in healthy infants: assessment by continuous esophageal aortic blood flow echo-Doppler.

Gueugniaud PY. Abisseror M. Moussa M. Godard J. Foussat C. Petit P. Dodat H.
Department of Anesthesiology, Edouard Herriot Hospital, CHU of Lyon, France.
Cardiovascular changes due to pneumoperitoneum during laparoscopic surgery are established in adult patients, but not known in infants. We investigated the hemodynamic effects of laparoscopy during general anesthesia in 12 ASA physical status I infants by using noninvasive continuous esophageal aortic blood flow (ABF) echo-Doppler monitoring. During the laparoscopic procedure, intraabdominal pressure was maintained automatically at 10 mm Hg by a CO2 insufflator, and minute ventilation was adjusted to avoid hypercapnia. Hemodynamic changes were continuously recorded on soft magnetic support and assessed at three time intervals: t0 (after the initiation of anesthesia), t1 (5 min after peritoneal insufflation), and t2 (5 min after exsufflation). The induction of pneumoperitoneum resulted in a significant decrease in ABF and stroke volume, and in a significant increase in systemic vascular resistance, compared with control values: 67% +/- 9% (P < 0.001), 68% +/- 10% (P < 0.001), and 162% +/- 34% (P < 0.001), respectively. These changes were completely reversed after peritoneal exsufflation. Pneumoperitoneum caused no significant changes in mean arterial pressure or in end-tidal CO2 pressure. These findings demonstrate that laparoscopy is associated with hemodynamic changes without clinically deleterious consequences in healthy infants during a short duration of pneumoperitoneum. Implications: The peritoneal insufflation achieved during laparoscopic surgery is associated with cardiovascular impairments (decrease in cardiac performance and increase in vascular resistance). We found that these changes had no clinically deleterious effects in healthy infants.

Pneumoperitoneum as a risk factor for endobronchial intubation during laparoscopic gynecologic surgery.

Lobato EB. Paige GB. Brown MM. Bennett B. Davis JD.
Department of Anesthesiology, University of Florida, Gainesville 32610-0254, USA.
Patients undergoing gynecological surgery under laparoscopic guidance usually receive general anesthesia with endotracheal intubation and mechanical ventilation. The creation of a pneumoperitoneum and the Trendelenburg position, both of which are used to improve visualization, are associated with cephalad movement of the diaphragm. This may increase the risk of endobronchial intubation. We studied the change in the distance from the tip of the endotracheal tube (ETT) to the carina with a fiberoptic bronchoscope in 30 patients aged 21-40 yr who were undergoing laparoscopic tubal ligation (n = 28) or hysterectomy (n = 2). Measurements were taken in the supine and Trendelenburg positions before and after pneumoperitoneum. The average distance from the ETT to the carina in the supine position was 2.1 +/- 0.8 cm and in the Trendelenburg position was 1.8 +/- 0.8 cm (P = not significant). After insufflation of the abdominal cavity, the mean distance decreased to 0.7 +/- 1.4 cm in the supine position (P < 0.05) and was associated with endobronchial intubation in eight patients. The addition of the Trendelenburg position to an established pneumoperitoneum resulted in minimal displacement (0.54 +/- 1.4 cm, P < 0.05) and one additional endobronchial intubation. We conclude that the insufflation of gas in the abdominal cavity, and not the change in patient position, is the main risk factor for endobronchial intubation in patients undergoing laparoscopic gynecologic surgery. Implications: This study demonstrated that in anesthetized women, the insufflation of gas into the abdomen during laparoscopy for gynecologic surgery is the main risk factor for migration of the endotracheal tube into a bronchus.

Prevention of postoperative nausea and vomiting with a combination of granisetron and droperidol.

Year 1998
Fujii Y. Toyooka H. Tanaka H.
Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan.
In this randomized, double-blind study, we compared the efficacy and safety of granisetron plus droperidol with each antiemetic alone for preventing postoperative nausea and vomiting (PONV) in 150 female patients scheduled for elective major gynecological surgery. Patients were randomly assigned to receive i.v. either granisetron 2.5 mg (Group G), droperidol 1.25 mg (Group D), or granisetron 2.5 mg plus droperidol 1.25 mg (Group GD) immediately before the induction of anesthesia (n = 50 in each group). A standard anesthetic technique and postoperative analgesia were used. Complete response, defined as no PONV and no administration of rescue antiemetic medication during the first 24 h after anesthesia, was 84% in Group G, 54% in Group D, and 96% in Group GD (P = 0.046 versus Group G, P = 0.001 versus Group D). No clinically important adverse effects were observed in any group. In conclusion, the combination of granisetron and droperidol is more effective than each antiemetic alone for complete response in patients undergoing general anesthesia for major gynecological surgery. IMPLICATIONS: We compared the efficacy of granisetron plus droperidol with each antiemetic alone for the prevention of nausea and vomiting after gynecological surgery. The granisetron/droperidol combination was the most effective against these emetic symptoms.

Tropisetron for treating established postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled study.

Year 1998
Alon E. Buchser E. Herrera E. Christiaens F. De Pauw C. Ritter L. Hulstaert F. Grimaudo V.
Anesthesiology Department of Zurich University Hospital, Switzerland.
Tropisetron can prevent postoperative nausea and vomiting (PONV) at doses smaller than those used to control chemotherapy-induced nausea and vomiting. In this placebo-controlled study, the efficacy and tolerability of three different doses of tropisetron were compared for the treatment of established PONV after surgical procedures in general anesthesia. Of 1513 patients who satisfied inclusion criteria, 314 experiencing PONV during the first 2 h after recovery from anesthesia were treated with one of three different doses of tropisetron (0.5, 2, or 5 mg) or placebo, administered i.v. as a single dose. Patients were then observed during 24 h for efficacy and tolerability. All three doses of tropisetron were significantly better than placebo in controlling emetic episodes and in reducing the need for rescue treatment. There were no significant differences among the three doses. However, in the subgroup of patients who had previous PONV, and in those randomized for nausea alone, the 2-mg and 5-mg doses controlled emetic episodes better than the 0.5-mg dose. All studied doses of tropisetron were well tolerated and did not affect vital signs. We conclude that a single i.v. administration of tropiestron significantly reduces the recurrence of emetic episodes in patients with established PONV after elective surgery with general anesthesia. Its optimal dose seems to be 2 mg. IMPLICATIONS: Three hundred-fourteen patients suffering from postoperative nausea and vomiting received different i.v. doses of a new antiemetic drug, tropisetron, to determine the lowest effective dose. We found that a single i.v. administration of tropisetron significantly reduced postoperative nausea and vomiting after elective surgery with general anesthesia.

Gastroesophageal reflux and tracheal contamination during laparoscopic cholecystectomy and diagnostic gynecological laparoscopy.

Year 1998
Doyle MT. Twomey CF. Owens TM. McShane AJ.
Department of Anesthesia & Intensive Care, St. Vincent's Hospital, Elm Park, Dublin, Ireland.
Laparoscopy causes an increase in intraabdominal pressure and may lead to an increase in gastroesophageal reflux (GER). We designed this study to assess and compare the frequency of GER and tracheal contamination in patients undergoing laparoscopic cholecystectomy (LC) and gynecological laparoscopy (LG). We studied 20 LC and 17 LG patients. The pH was measured using monocrystalline antimony pH electrodes positioned in the middle to upper esophagus and on the posterior wall of the trachea distal to the tip of the endotracheal tube. Acid reflux was defined as a decrease in esophageal pH to 4.0 or less. Alkaline reflux was defined as an abrupt increase in esophageal pH of more than 1.0, not associated with previous acid reflux. More than 80% of all patients at baseline had a gastric pH < or = 2. Overall, acid GER alone occurred in 47% patients in the LG group and in 15% patients in the LC group. During recovery, a larger proportion of patients had acid reflux in the LG group (47%) than in the LC group (10%). In contrast, alkaline reflux occurred in 75% of LC patients and 11.7% of LG patients. After cholecystectomy, there is an acute increase in the incidence of alkaline reflux. This alkaline reflux may be due to duodenogastric reflux resulting in an alkaline gastric shift. IMPLICATIONS: We studied the incidence of reflux of stomach contents in patients undergoing laparoscopic (keyhole) surgery for cholecystectomy or gynecology, using pH probes in the esophagus (gullet) and the trachea (windpipe). Acid reflux was very common but did not pass into the trachea. After gallbladder removal, the refluxed material became alkaline.

Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation.

Year 1998
Kettner SC. Gonano C. Seebach F. Sitzwohl C. Acimovic S. Stark J. Schellongowski A. Blaicher A. Felfernig M. Zimpfer M.
Department of Anesthesiology and General Intensive Care, University of Vienna, Austria. stephan.kettner@akh-wien.ac.at
Orthotopic liver transplantation (OLT) is associated with severe bleeding, especially after reperfusion of the grafted liver. Heparin released from the liver graft contributes to postreperfusion coagulopathy. Although patients with liver cirrhosis have increased levels of endogenous heparinoids, the role of these substances during liver transplantation is unclear. Therefore, we performed native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping of the vena cava, 10 min before and 10 min after graft perfusion, and at the end of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin activity. In contrast to other investigations, we found significant heparin effects before reperfusion, although patients received no exogenous heparin. These heparin effects were greater in patients with cirrhosis compared with patients with cancer as the underlying disease leading to OLT. Administration of coagulation factors is the usual treatment of coagulopathies during OLT. The comparison of native versus heparinase-modified TEG can distinguish between heparin activity or coagulation factor deficiency as a cause of bleeding complications and provides a rational approach to the treatment of bleeding during OLT. Implications: Impaired coagulation function, contributed to by heparin or heparin-like substances, is frequently observed after reperfusion of a transplanted liver. This study demonstrates that a heparinase-modified thrombelastography can identify significant heparin effects in the absence of exogenous heparin administration in patients undergoing liver transplantation.

A comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. S3A-409 and S3A-410 Study Groups.

Year 1998
Fortney JT. Gan TJ. Graczyk S. Wetchler B. Melson T. Khalil S. McKenzie R. Parrillo S. Glass PS. Moote C. Wermeling D. Parasuraman TV. Duncan B. Creed MR.
Department of Anesthesiology, Duke University, Durham, North Carolina 27710, USA.
Two identical, randomized, double-blind, placebo-controlled studies enrolled 2061 adult surgical outpatients at high risk of postoperative nausea and vomiting (PONV) to compare i.v. ondansetron 4 mg with droperidol 0.625 mg and droperidol 1.25 mg for the prevention of PONV. The antiemetic drugs or placebo were administered i.v. 20 min before the induction of anesthesia with a barbiturate compound, followed by maintenance with N2O/isoflurane/enflurane. Nausea, emetic episodes, adverse events, and patient satisfaction were analyzed for the 0 to 2 h and 0 to 24 h postoperative periods. In the 0 to 2 h postoperative period, there was a complete response (no emesis or rescue antiemetic) in 46% of subjects given placebo (P < 0.05 versus antiemetic groups), in 62% given ondansetron, in 63% given droperidol 0.625 mg, and in 69% given droperidol 1.25 mg (P < 0.05 versus ondansetron). In the 0 to 24-h postoperative period, there were no significant differences in complete response between the ondansetron and droperidol 0.625 or 1.25 mg groups; all groups remained superior to placebo. The proportion of patients without nausea during the 0 to 24 h postoperative period was greater in the antiemetic groups compared with the placebo group; however, droperidol 1.25 mg was more effective than ondansetron 4 mg or droperidol 0.625 mg (43% vs 29% or 29%, respectively). Headache incidence was higher in the ondansetron group compared with either droperidol group. Patient satisfaction scores did not differ significantly among antiemetic treatment groups, although all were superior to placebo. In conclusion, all antiemetic treatment regimens were superior to placebo for the prevention of PONV in the immediate postoperative period; however, droperidol 1.25 mg was more efficacious than ondansetron during the early recovery period (0-2 h). There were no significant differences between ondansetron and either droperidol dose for emesis prevention during the 0 to 24 h postoperative period. Implications: More than 2000 patients at high risk of postoperative nausea and vomiting were given either placebo, ondansetron 4 mg, or droperidol 0.625 mg or 1.25 mg i.v. before the administration of general anesthesia. After surgery, the incidence of nausea, vomiting, medication side effects, and patient satisfaction were evaluated for 24 h. Droperidol 0.625 or 1.25 mg i.v. compared favorably with ondansetron 4 mg i.v. for the prevention of postoperative nausea and vomiting after ambulatory surgery.

Symptom distress and functional status changes during the first seven days after ambulatory surgery.

Year 1998
Swan BA. Maislin G. Traber KB.
Department of Anesthesia, University of Pennsylvania School of Nursing, Philadelphia, USA.
In this study, we describe changes in symptom distress and functional status 24 h, 4 days, and 7 days after ambulatory surgery. Adult patients aged 18-64 yr, ASA physical status I-III, were studied. The General Symptom Distress Scale was used to score 11 general symptoms; scores range from 0 (no symptoms present) to 4 (symptoms present, constant, cannot be ignored, and, in a 24-h period, remained distressing for more than half the time). The Functional Status Questionnaire was used to evaluate basic and intermediate activities of daily living. Procedure-specific analyses of covariance were performed using multiple linear regression analyses. These models were used to obtain estimates of change while adjusting for preoperative index values of age, ASA physical status, type of anesthesia, and study site. Models for hernia (n = 41) and laparoscopy (n = 59) procedures used F statistics to test the overall significance of the model. Symptom distress persisted until the 7th postoperative day after ambulatory surgery. Patients experienced decreased functional status during the first 7 postoperative days, especially after hernia repair. Older laparoscopy patients tended to have more symptom distress and decreased functional status than younger patients. Only 22% of patients had returned to full- or part-time work by the 7th postoperative day. We conclude that although major morbidity is uncommon after ambulatory surgery, symptom distress and reduced functional status are common 7 days postoperatively. Implications: Previous studies of patient status after ambulatory surgery have focused on mortality, major morbidity, and unanticipated hospitalization. In this study, we examined clinically significant but less life-threatening patient outcomes. Important problems in ambulatory surgery are posed by complications that occur at home. Careful assessment of discharge criteria is important to avoid these problems in this growing patient population.

Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption.

Year 1998
Chia YY. Liu K. Liu YC. Chang HC. Wong CS.
Department of Anesthesia, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China. yychia@isca.vghks.gov.tw
We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. Implications: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.

A new and simple maneuver to position the left-sided double-lumen tube without the aid of fiberoptic bronchoscopy.

Year 1998
Bahk JH. Oh YS.
Department of Anesthesiology, Seoul National University College of Medicine, Korea. bahkjh@plaza.snu.ac.kr
The double-lumen tube (DLT) is the mainstay of one-lung ventilation (OLV). We sought to determine whether this new intubation maneuver using an endobronchial cuff pressure could be substituted for verification by fiberoptic bronchoscope (FOB) in most conditions requiring left-sided DLT. Seventy-nine patients requiring video-assisted thoracoscopic surgery for pneumothorax or mediastinal mass, or open thoracotomy for lung or esophageal cancer were enrolled in this study. We used 35F (n = 23), 37F (n = 51), or 39F (n = 5) disposable polyvinyl chloride DLTs (Broncho-Cath; Mallinckrodt Medical Ltd., Athlone, Ireland), depending on the height and gender of the patients. The DLTs were inserted deeply until resistance was felt. At that time, the pilot of the endobronchial cuff was connected to the Control-Inflator (VBM Medizintechnik GmbH, Sulz am Neckar, Germany) via a three-way stopcock. The bronchial balloon was inflated with 1.0-2.0 mL of air through the stop-cock until approximately 30 cm H2O of cuff pressure was obtained. The DLT was slowly withdrawn until the pressure of the Control-Inflator decreased to approximately half the peak pressure during the initial phase of removal. At that time, the bronchial balloon was deflated, and the DLT was advanced approximately 1.0 cm (1.5 cm for the 39F DLT); using FOB, its position was checked by an independent observer not involved in positioning the DLTs. The ideal position was defined as that in which the carina was located at the same level with the middle 5 mm between the proximal margin of the endobronchial balloon and the circumferential black mark. In 50 patients the position was ideal, and in 27 patients it was not ideal but was within the margin of the safety. There were only two failures. We conclude that if a FOB is unavailable or inapplicable, this simple and new maneuver may be used as a substitute during the positioning of DLTs. Implications: The correct position of the double-lumen tube is vital for one-lung ventilation, which has been confirmed with a fiberoptic bronchoscope. We devised a simple maneuver to position the double-lumen tube correctly without a fiberoptic bronchoscope.

A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis.

Year 1998
Cook-Sather SD. Tulloch HV. Cnaan A. Nicolson SC. Cubina ML. Gallagher PR. Schreiner MS.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Pennsylvania 19104-4399, USA.
This prospective, nonrandomized, observational study of 76 infants with pyloric stenosis was conducted at an academic children's hospital and compared awake versus paralyzed tracheal intubation in terms of successful first attempt rate, intubation time, heart rate (HR) and arterial hemoglobin oxygen saturation (SpO2) changes, and complications. Three groups were determined by intubation method: awake (A) with an oxygen-insufflating laryngoscope, after rapid-sequence induction (R), or after modified rapid-sequence induction (M) including ventilation through cricoid pressure. Successful first attempt intubation rate was 64% for Group A versus 87% for paralyzed Groups R and M (P = 0.028). Median intubation time was 63 s in Group A versus 34 s in Groups R and M (P = 0.004). Transient, mild decreases in mean HR and SpO2 and incidences of significant bradycardia and decreased SpO2 did not vary by group. Complications, including bronchial or esophageal intubation, emesis, and oropharyngeal trauma, were few. Senior anesthesiologists intervened in four tracheal intubations. We advocate anesthetized, paralyzed tracheal intubation because struggling with conscious infants takes longer, often requires multiple attempts, and prevents neither bradycardia nor decreased SpO2. After induction, additional mask ventilation with O2 confers no advantage over immediate tracheal intubation in preserving SpO2. Implications: In our children's hospital, awake tracheal intubation was not superior to anesthetized, paralyzed intubation in maintaining adequate oxygenation and heart rate or in reducing complications, and should be abandoned in favor of the latter technique for routine anesthetic management of otherwise healthy infants with pyloric stenosis.

Cerebral blood flow velocity in patients with subclinical portal-systemic encephalopathy.

Year 1998
Katz JJ. Mandell MS. House RM. Bilir BM. Barton B. Zamudio S.
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver 80262, USA.
Alterations in cerebral blood flow (CBF) are implicated in the etiology of portal-systemic encephalopathy. We hypothesized that CO2 reactivity of the cerebral circulation may be impaired in subjects with chronic liver disease (CLD) who also had subclinical portal-systemic encephalopathy (SPSE). We compared the relationship between PETCO2 and cerebral blood flow velocity in 10 patients with CLD with those of 10 healthy control subjects. Middle cerebral artery mean blood flow velocity (MCAMFV) was measured using transcranial Doppler during rest, hyperventilation, and hypoventilation. The degree of SPSE was quantified by using psychometric testing. Patients with CLD had poorer psychometric test scores compared with control subjects. Patients with CLD had lower PETCO2, MCAMFV, and blood pressure values and higher heart rates, differing from control subjects in all ventilation states. However, CO2 reactivity, the rate of change in MCAMFV to changes in ventilation (expressed as percent change in CBF velocity per mm Hg change in PETCO2) was similar for both groups (4.6% +/- 0.6% vs 4.2% +/- 0.5% for patients with CLD versus control subjects, P = 0.15). Implications: Psychometric test scores in patients with chronic liver disease revealed subclinical impairment compared with control subjects. Transcranial Doppler measurements of middle cerebral artery blood flow with varying PETCO2 were conducted, but the CO2 response of patients with liver disease was within the range of control subjects.