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* From the Divisions of Cardiovascular Anesthesia, University Hospital of Zürich,
Zürich; and the University Hospital of Lausanne, Lausanne, Switzerland.
Address correspondence to: Dr. Dominique A. Bettex, Division of Cardiovascular Anesthesia, USZ - Rämistrasse 100, CH – 8091 Zürich, Switzerland. Phone: +41 1 255 59 33; Fax: +41 255 45 61; E-mail: dominique.bettex{at}ifa.usz.ch
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Methods: Twenty-four consecutive patients with normal cardiopulmonary function who were scheduled for elective cardiac surgery were randomized to receive either a continuous iv infusion of sufentanil 0.9 to 1.8 µg•kg-1•min-1 (13 patients), or a single lumbar intrathecal dose of sufentanil 50 µg and morphine 500 µg (11 patients). We prospectively studied perioperative analgesia, time to extubation and early postoperative maximal inspiratory capacity in the two groups. In the intensive care unit, the medical and nursing staff were blinded to the analgesic technique.
Results: Intrathecal sufentanil morphine allowed a shorter duration of intubation (104 ± 56.5 min vs 213 ± 104 min; P = 0.01), reduced the need for postoperative analgesia with nicomorphine (equipotent to morphine) (0.7 ± 0.4 mg•hr-1 vs 1.2 ± 0.4 mg•hr-1; P = 0.008) and improved postoperative maximal inspiratory capacity (53.4 ± 16.1 vs 38.4 ± 12.5% of the norm; P = 0.05).
Conclusion: In low-risk patients undergoing coronary artery bypass graft or valve surgery, combined intrathecal sufentanil and morphine with a target-controlled infusion of propofol satisfies the goals of fast-track cardiac surgery.
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Intrathecal (IT) analgesia entails a lower risk of hematoma formation than epidural access.6 IT morphine allows intense postoperative analgesia but does not cover the operative period and may cause prolonged ventilatory depression.7 IT sufentanil provides intense and fast-onset analgesia8 and, along with IT morphine, appears to be a suitable choice for fast-track cardiac surgery.9
The aim of this prospective randomized study was to assess the effect of intraoperative combined IT sufentanil and morphine in comparison to low-dose iv sufentanil in low-risk patients undergoing elective cardiac surgery. Both anesthetic techniques were combined with a target-controlled infusion of propofol.
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Anesthesia protocol
Preoperative medications, except angiotensin-converting enzyme inhibitors, diuretics and digoxin, were continued until the morning of surgery. One to two hours before induction of anesthesia, all patients received either oral flunitrazepam (1–2 mg) or midazolam (7.5–15 mg). Prior to arrival in the operating room, every patient was randomized using a classical table of random numbers (Geigy Scientific Tables) to receive either IT sufentanil and morphine (IT group) or iv sufentanil (iv group).
Routine monitoring was instituted initially with 5-lead electrocardiography (ECG), pulse oximetry (SpO2) and radial artery pressure. Patients in the IT group were then turned on their sides, and after standard sterile preparation, a lumbar puncture at the L3–L4 or L2–L3 level was performed, with the use of a 25-gauge Quincke-tipped spinal needle (Sprotte Standard Needle, Pajunk, Germany). Every lumbar puncture was done by the same anesthesiologist, and no more than three attempts were allowed. Once clear cerebrospinal fluid was obtained, preservative-free sufentanil 50 µg and morphine 500 µg diluted in 6 mL of sodium chloride were injected into the IT space and the needle removed. The patients were brought into the dorsal decubitus position and anesthesia induced with a target-controlled infusion of propofol (TCI-propofol; beginning with a target dose of 1.5 µg•mL-1 and gradually increasing, according to patient hemodynamic response, to a maximal target dose of 3 µg•mL-1), pancuronium 0.1 mg•kg-1 and a bolus dose of iv sufentanil 0.5 µg•kg-1. The time between lumbar puncture and anesthesia induction was kept as short as possible, to avoid patient discomfort through the early appearance of pruritus, thoracic rigidity or respiratory depression secondary to IT sufentanil. Maintenance of anesthesia was ensured with TCI-propofol; no further iv opioids were given. Anesthesia in patients in the iv group was induced with TCI-propofol (target dose, 1.5–3 µg••mL-1), pancuronium 0.1 mg•kg-1 and a bolus dose of iv sufentanil 1 µg•kg-1. Continuous infusion of sufentanil was then begun: 1.8 µg•kg-1•hr-1 until CPB, followed by 0.9 µg•kg-1•hr-1 until closure of the chest. The use of vasoactive substances as well as the occurrence of ECG changes, arrhythmia or hemodynamic variations of more than 20% of the awake values were observed by an independent anesthesiologist and recorded.
After endotracheal intubation and initiation of mechanical ventilation (Servo C, Siemens-Elema AB, Sweden), a three-lumen central venous catheter (Arrow-Howes 7F, Arrow International; Erding, Germany), a percutaneous sheath introducer set (8.5F, Arrow International) and a continuous cardiac output pulmonary catheter (Swan-Ganz CCO/VIP 7.5F, Baxter; Unterschleissheim, Germany) were inserted in the right internal jugular vein in both groups. Before aortic cannulation, bovine heparin 300 IU•kg-1 was administered intravenously and the CPB was started when a minimal activated clotting time (ACT) of 300 sec was reached (Medtronic Hemotec, Inc. Parker, CO, USA). During CPB, an ACT 500 sec was maintained. Following initiation of CPB, patients were cooled to a minimum rectal temperature of 32°C and were later rewarmed to 36°C before being taken off bypass. The use of vasoactive drugs was left to the discretion of the attending anesthesiologist. Heparinization was reversed with an initial 1:100 protamine iv dose (1 mg for 100 IU of heparin administered). An additional dose of 0.5 to 1 mg•kg-1 of protamine was given when the ACT remained above 140 sec.
Postoperative management
After surgery, patients were transferred to the ICU. The medical and nursing staff of the ICU were blinded to the anesthetic technique. A continuous infusion of propofol (0.5 to 1 mg•kg-1•hr-1) was maintained until normothermia, hemodynamic stability and minimal chest tube drainage (< 100 mL•hr-1) were attained. For acute pain control prior to extubation, the nursing staff administered an iv bolus of nicomorphine (increments of 2 mg) as required. Nicomorphine is known to be equipotent to morphine but should induce less adverse effects such as respiratory depression, pruritus, nausea and vomiting. Ibuprofen 400 mg was given rectally or orally three times a day. Forced air warming was used to maintain core temperature above 36°C and shivering was treated with iv meperidine (12.5–25 mg). The criteria for extubation included normal neurologic status, stable hemodynamics under minimal inotropic support (< 5 µg•kg-1•min-1 dopamine or dobutamine), adequate pulmonary function (spontaneous ventilation for a minimum of 30 min with a vital capacity > 12 mL•kg-1, respiratory rate between 10 and 20 min-1, PaCO2 < 50 mmHg, pH > 7.30 and PaO2 > 75 mmHg on a FIO2 < 40%) and minimal chest tube drainage (< 100 mL•hr-1). After extubation, the patients used a patient-controlled analgesia device with nicomorphine (iv bolus of 2 mg every eight minutes, maximum).
A two-hour sedation score using the Ramsay scale11 and a four-hour analgesic score [visual analogue scale (VAS), 1–10] was recorded by the nurses in the ICU. Patients were questioned regarding the occurrence of pruritus, nausea and vomiting as well as intraoperative awareness. The times between ICU admission and extubation and between cessation of propofol infusion and extubation were recorded as well as the maximal inspiratory capacity on the first postoperative day (Coach 2 breathing exerciser, DHD Healthcare, New York, NY, USA). The latter value was normalized to the expected value considering the size and age of the patient12 and compared with the preoperative value of FEV1 and of Tiffenau ratio, both also normalized to the expected value.
ICU discharge criteria included patient orientation, hemodynamic stability without the use of iv vasoactive substances, SpO2 > 90% with nasal O2 at less than 4 L•min-1 and urine output > 0.5 mL•kg-1•hr-1. Chest tubes, pulmonary catheter and arterial lines were removed before transfer to the ward.
Statistics
The primary outcome measurements were duration of intubation, postoperative analgesia requirements and postoperative spirometry. Results are expressed as the mean ± SD (range), unless otherwise indicated. Operative and postoperative variables were compared by means of the Mann-Whitney U test for continuous variables and Fischer’s exact test for nominal variables. P < 0.05 was considered significant.
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) and preoperative medications. Surgical data including type of procedure, duration of CPB and aortic cross-clamping, were also similar between groups (Table II).
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). The use of vasoactive substances and the occurrence of ST segment changes, hypotension or arrhythmia during induction (Table II), were not significantly different between the two groups. The occurrence of hypertension during induction, defined as more than 20% augmentation of mean basal arterial pressure, was significantly more frequent in the IT group. The occurrence of hypotension during induction, defined as more than 20% reduction of mean basal arterial pressure was similar in both groups. The CPB and post-CPB periods were uneventful for all patients and intraoperative surgical complications did not occur. Two patients (one in each group) received dopamine (1–2.5 µg•kg-1•min-1), and one patient in the iv group received dobutamine (5 µg•kg-1•min-1) to facilitate separation from bypass (Table II).
Extubation, postoperative analgesia and complications
Postoperative risk scores (APACHE II;14 Table III) and use of vasoactive drugs were similar in both groups. The trachea could not be extubated in seven patients (three in the IT group and four in the iv group) within the first six hours after operation: three because of hemodynamic instability or postoperative ST segment changes (one patient in the IT group following aortic valve replacement and one in each group following CABG surgery), one in the iv group because of hypothermia at ICU admission (34.4°C), one in the IT group because of mediastinal bleeding requiring rethoracotomy and two in the iv group because of delayed awakening and/or respiratory depression. The maximal duration of intubation was nine hours and 15 min. The sedation score was significantly lower in the iv group after two hours but was comparable between groups after four hours (Table III). The time from ICU admission to extubation and the time between cessation of sedation and extubation were significantly higher in the iv group (Table III). No patient required reintubation. The need for iv nicomorphine was significantly higher in the iv group even though the two groups’ VAS scores were not significantly different (Figure 1). Five patients suffered from nausea or vomiting (three in the IT group and two in the iv group), and one patient complained of pruritus (IT group).
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). There was no perioperative myocardial infarction (defined as troponine, creatine kinase or creatine kinase-MB elevation or new Q-wave on the ECG). According to the routine in our institution, every patient stayed overnight in the ICU for monitoring purposes; ICU duration of stay was the same in both groups.
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Choice and advantages of the method used
Recent evidence suggests that fast-track cardiac surgery is not only safe but may improve patient outcome by decreasing the incidence of postoperative cardiopulmonary morbidity and may lower the cost of cardiac surgery.1–3,9 The optimal anesthetic technique to reach this goal remains debatable. TCI-propofol offers stable hemodynamics with minimal negative inotropism and a rapid and controlled recovery; it is widely used for noncardiac as well as cardiac surgery.15 Because of its previously demonstrated advantages for fast-track cardiac surgery,3 we chose TCI-propofol for induction and maintenance of anesthesia.
Previous studies have shown that although IT morphine prior to cardiac surgery provides profound postoperative analgesia16,17 it does not offer sufficient intraoperative analgesia because of its delayed peak of action. Concerns have been raised regarding the potential for ventilatory depression and delayed extubation when IT morphine is used as part of a fast-tracking program, especially with the concomitant use of iv analgesics and sedatives.8,18,19 IT sufentanil is known to provide an intense and fast-onset analgesia.8,9 We postulated that the combination of IT morphine and sufentanil could avoid deleterious effects and increase patient comfort because of their different peaks of activity.8,16,17
In our study, the combination of IT morphine and sufentanil provided effective intraoperative analgesia. The trend toward hypertension during induction in the spinal group did not result in increased requirements for vasoactive substances because of its non-sustained nature. There was no need for iv opioids except shortly before intubation when IT sufentanil is not active.9 The IT group required significantly more iv propofol, however, probably because they received less iv sufentanil, which has its own sedative effect.20 The time to extubation was significantly shorter in the IT group despite a similar time between ICU admission and time of adequate answer to simple command. We attribute this to the larger amount of iv sufentanil and nicomorphine required in the iv group. None of the patients who remained intubated for more than six hours had respiratory problems related to IT opioids. Actually, only two of the seven patients with slightly prolonged intubation times required a longer intubation because of delayed awakening or respiratory depression; they both belonged to the iv group. The five other patients suffered from hemodynamic instability or bleeding complications, which were not likely related to anesthetic technique.
Postoperative comfort
IT morphine and sufentanil provided effective postoperative analgesia, as indicated by a significant decrease in the need for postoperative iv nicomorphine in the IT group for comparable VAS analgesia scores. The well-known side effects of IT opioids, besides ventilatory depression, are pruritus, nausea, vomiting and urinary retention. None of the patients experienced severe pruritus; the incidence of nausea and vomiting was similar in both groups, and no patient experienced urinary retention after removal of the urinary catheter or ventilatory depression after tracheal extubation. We used iv propofol for ICU sedation as it is known to facilitate the process of weaning patients from mechanical ventilation after cardiac surgery when compared with midazolam.21 The low incidence of postoperative opioid-related nausea and vomiting could be attributed to the antiemetic effect of propofol.22
Risk of IT analgesia
Although extremely rare, subarachnoid and epidural hematomas have occurred in patients when a diagnostic or therapeutic lumbar puncture was followed by systemic heparinization.23 None of the previous reports of the use of IT morphine for cardiac surgery have indicated the development of subarachnoid or epidural hematoma.7,19,24 However, usual precautions should be followed to decrease this risk.24 Our exclusion criteria with respect to this potential complication were particularly strict, and we were ready, in agreement with the surgeons, to delay surgery in case of a bloody tap (which did not occur). The minimal delay between lumbar puncture and heparinization was 64 min, which is close to the 70 min previously reported by Chaney et al.7 This delay might have clinical relevance upon intradural hematoma formation but this remains unclear. We observed no clinical evidence of central neuraxial hematoma in any patient enrolled in our study, but our series is obviously too small to infer the safety of this method.
Study limitations
Limitations include a predominantly male population, a small sample size, and a nonuniform type of surgery. Female sex may impart additional operative risk in CABG surgery25 and was an adverse risk factor for early extubation univariately in one study and multivariately in another.26,27 Although sex-related differences in pain perception as well as response to pain have been described,28 we are not aware of a sex-linked difference in the effect of spinal analgesia. The difficulty recruiting patients was predictable because patients taking aspirin were excluded. A recently adopted policy in our institution is to continue aspirin until the day of surgery, so this change forced us to stop the study. The type of cardiac surgery, with the exception of minimally invasive procedures, does not appear to have a significant influence on intubation time, suggesting that patients undergoing valve repair or replacement are not at increased risk for delayed extubation.10
The optimal dose of IT sufentanil and morphine has not been determined and should remain the subject of future studies. The beneficial effects on immediate postoperative ventilatory function documented in our study should be investigated in patients with poor preoperative ventilatory function before the use of IT sufentanil and morphine for fast-track cardiac surgery in this type of patient can be recommended.
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Revision received May 29, 2002. Accepted for publication February 26, 2002.
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2 Cheng DCH, Karski J, Peniston C, et al. Early tracheal extubation after coronary artery bypass graft surgery reduces costs and improves resource use. A prospective, randomized, controlled trial. Anesthesiology 1996; 85: 1300–10.[Medline]
3 D’Attellis N, Nicolas-Robin A, Delayance S, Carpentier A, Baron JF. Early extubation after mitral valve surgery: a target-controlled infusion of propofol and low-dose sufentanil. J Cardiothorac Vasc Anesth 1997; 11: 467–73.[Medline]
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5 Kirnö K, Friberg P, Grzegorczyk A, Milocco I, Ricksten SE, Lundin S. Thoracic epidural anesthesia during coronary artery bypass surgery: effects on cardiac sympathetic activity, myocardial blood flow and metabolism, and central hemodynamics. Anesth Analg 1994; 79: 1075–81.
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9 Swenson JD, Hullander RM, Wingler K, Leivers D. Early extubation after cardiac surgery using combined intrathecal sufentanil and morphine. J Cardiothorac Vasc Anesth 1994; 8: 509–14.[Medline]
10 London MJ, Shroyer AL, Coll JR, et al. Early extubation following cardiac surgery in a veterans population. Anesthesiology 1998; 88: 1447–58.[Medline]
11 Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 656–9.
12 Ruppel G. Manual of Pulmonary Function Testing, 6th ed. St-Louis: Mosby, 1994: 461.
13 Nashef SAM, Roques F, Michel P, et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999; 16: 9–13.
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18 Bailey PL, Lu JK, Pace NL, et al. Effects of intrathecal morphine on the ventilatory response to hypoxia. N Engl J Med 2000; 343: 1228–34.
19 Alhashemi JA, Sharpe MD, Harris CL, Sherman V, Boyd D. Effect of subarachnoid morphine administration on extubation time after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000; 14: 639–44.[Medline]
20 Kugler J, Grote B, Laub M, Doenicke A, Dick E. The hypnotic effect of fentanyl and sufentanil. An electro-encephalographic comparison (author’s transl; German). Anaesthesist 1977; 26: 343–8.[Medline]
21 Searle NR, Cote S, Taillefer J, et al. Propofol or midazolam for sedation and early extubation following cardiac surgery. Can J Anaesth 1997; 44: 629–35.
22 Gan TJ, El-Molem H, Ray J, Glass PSA. Patient-controlled antiemesis. A randomized, double-blind comparison of two doses of propofol versus placebo. Anesthesiology 1999; 90: 1564–70.[Medline]
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25 Christakis GT, Weisel RD, Buth KJ, et al. Is body size the cause for poor outcomes of coronary artery bypass operations in women? J Thorac Cardiovasc Surg 1995; 110: 1344–56.
26 Arom KV, Emery RW, Petersen RJ, Schwartz M. Cost-effectiveness and predictors of early extubation. Ann Thorac Surg 1995: 60: 127–32.
27 Habib RH, Zacharias A, Engoren M. Determinants of prolonged mechanical ventilation after coronary artery bypass grafting. Ann Thorac Surg 1996; 62: 1164–71.
28 Sun LS. Gender differences in pain sensitivity and responses to analgesia. J Gend Specif Med 1998; 1: 28–30.
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