- Email: [email protected]
The effects of intrathecal morphine on patients undergoing minimally invasive direct coronary artery bypass surgery
The Effects of Intrathecal Morphine on Patients Undergoing Minimally Invasive Direct Coronary Artery Bypass Surgery Eliyahu Zisman, MD,* Alexander Shenderey, MD,* Ron Ammar, MD,† Arieh Eden, MD,* and Reuven Pizov, MD* Objective: To evaluate the effects of intrathecal morphine (ITM) on the perioperative use of opiates and the fast-track pathway in patients undergoing minimally invasive direct coronary artery bypass grafting (MIDCAB). Design: Retrospective cohort study. Settings: University teaching hospital. Participants: Twenty-two elective consecutive patients who underwent MIDCAB surgery. Interventions: Eleven patients received an intrathecal injection of morphine, 7 g/kg (ITM group, n ⴝ 11), and the control group (n ⴝ 11) received standard anesthesia care. Measurements and Main Results: The intraoperative dose of fentanyl was 0.55 ⴞ 0.2 mg in the ITM group and 1.1 ⴞ 0.2 mg in the control group (p < 0.0001). Four patients in the ITM group and none in the control group were extubated in the operating room. Extubation time was 3.2 ⴞ 4.7 hours in the ITM group and 6.3 ⴞ 3.4 hours in the control group (p ⴝ
0.016). Morphine requirements in 24 hours after surgery were 2.0 ⴞ 3.5 mg in the ITM and 16.1 ⴞ 4.8 mg in the control group (p < 0.0001). There were no differences in ischemic time, intraoperative fluid requirements, postoperative blood loss, and duration of surgical procedure. Hospital length of stay was shorter in the ITM group compared with the control group (3.9 ⴞ 1.7 days v 4.9 ⴞ 1.4 days, respectively, p ⴝ 0.047). Conclusions: ITM has to be considered in MIDCAB surgery as an effective component of the perioperative analgesia. The safety and effects of ITM in the patient’s recovery after MIDCAB surgery should be evaluated in further prospective studies. © 2005 Elsevier Inc. All rights reserved.
M
to the general anesthesia comprised the study group. They received 7 g/kg of preservative-free morphine sulfate before the induction of anesthesia. The control group consisted of 11 patients with a similar medical condition who did not consent to receive an intrathecal injection of morphine or when 2 attempts to perform spinal injection failed. For patients to be eligible to receive ITM (or to be included as controls) the following criteria were used: good left ventricular function (ejection fraction ⬎40%), no evidence of chronic obstructive pulmonary disease, normal coagulation profile (prothrombin time, partial thromboplastin time, fibrinogen, platelet count ⬎100,000/mL3), no history of abnormal bleeding, no intake of anticoagulation or antiplatelet medications besides aspirin, no abnormal lumbar spine anatomy or serious neurologic pathology, and primary coronary artery surgery (single grafting) without use of inotropic drugs or intra-aortic balloon pump before surgery. Patients in both groups were premedicated with oral oxazepam, 10 mg. Monitoring included 2-lead electrocardiogram with ST-analyzer, invasive blood pressure, central venous pressure, oral and rectal temperature, pulse oximetry, arterial blood gases, capnography, and urinary output. The patients in the ITM group received an intrathecal injection of 7 g/kg of preservative-free morphine sulfate through a spinal pencil-point 24-g needle before induction of general anesthesia. Only 2 attempts of intrathecal injection were permitted. If the spinal tap appeared bloody or the first 2 attempts failed, surgery proceeded with general anesthesia alone. Induction of anesthesia was the same in both groups and consisted of midazolam, fentanyl, propofol, succinylcholine, and insertion of a double-lumen endobronchial tube for separation of the lungs. Maintenance of anesthesia was performed using intravenous fentanyl (total dose up to 10 g/kg), midazolam (total dose up to 5 mg), pancuronium bromide (0.01mg/kg), and isoflurane as needed. An additional aliquot of fentanyl was given when no change was made in the dosage of hypnotics or isoflurane and the signs of pain appeared including increases in blood pressure and heart rate and tears. Particular efforts were made to keep the body temperature above 35°C during the surgery. Anticoagulation was achieved by injecting 100 U/kg of heparin. If the targeted activated coagulation time (300 seconds) was not reached, additional heparin was given. After the left anterior descending artery anastomosis was performed, protamine sulfate at a dose of 0.5 mg/kg was given to normalize the activated coagulation time below 170 seconds. At the end of the surgery, an attempt to extubate the patient in the operating room was performed according to the following criteria: the patient is nearly fully awake, muscle relaxants have been
INIMALLY INVASIVE direct coronary artery bypass surgery (MIDCAB) performed through a left thoracotomy has been suggested either for patients with 1-vessel coronary disease or for patients who are scheduled for a combined surgical and endovascular revascularization procedure. Although MIDCAB is a shorter and less extended procedure than conventional cardiac surgery, left thoracotomy, through which it is performed, is associated with costal trauma leading to significant postoperative pain.1,2 Effective perioperative pain control in patients undergoing MIDCAB is crucial during recovery and for application of a fast-track pathway.3-5 Intrathecal morphine administration is effective in controlling postoperative pain and has been used in cardiac surgery since 1980, despite the potential risk of dural puncture.6 Because of its lipophilic characteristic, morphine sulphate injected intrathecally, even at the lumbar level, produces widespread, effective analgesia.7 Spinal injection of opiates was shown to be more effective in postoperative pain control than the standard technique, but faster recovery was not observed.5,8-10 In this study, the authors compared the outcome of MIDCAB patients who received intrathecal morphine as an adjuvant to general anesthesia with those who received solely general anesthesia. METHODS Twenty-two consecutive patients scheduled for elective MIDCAB surgery took part in this retrospective cohort study. After detailed explanation about the neurologic risks of intrathecal injection, 11 patients who agreed to receive intrathecal morphine (ITM) in addition
From the Departments of *Anesthesiology and Critical Care Medicine and †Cardiothoracic Surgery, Carmel Lady Davis Medical Center, Haifa, Israel. Address reprint requests to Eliyahu Zisman, MD, Department of Anesthesiology and Critical Care Medicine, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel. E-mail: [email protected] © 2005 Elsevier Inc. All rights reserved. 1053-0770/05/1901-0007$30.00/0 doi:10.1053/j.jvca.2004.11.007 40
KEY WORDS: coronary artery surgery, MIDCAB, thoracotomy, intrathecal morphine, perioperative pain control
Journal of Cardiothoracic and Vascular Anesthesia, Vol 19, No 1 (February), 2005: pp 40-43
THE EFFECTS OF INTRATHECAL MORPHINE
41
Table 1. Demographic Data and Preoperative Morbidity Parameter
Control Group (n ⫽ 11)
ITM Group (n ⫽ 11)
p Value
Age (y) Weight (kg) Sex; male:female Myocardial infarction Hypertension Hyperlipidemia Renal failure CVA PVD Smoking Chronic atrial fibrillation
64.7 ⫾ 13.1 86.2 ⫾ 18.8 9:2 6 (55%) 11 (100%) 6 (55%) 2 (18%) 0 (0%) 1 (9%) 4 (36%) 0 (0%)
63.4 ⫾ 15.0 73.55 ⫾ 11.7 9:2 4 (36%) 5 (45%) 6 (55%) 2 (18%) 1 (9%) 1 (9%) 3 (27%) 1 (9%)
NS NS NS NS 0.012 NS NS NS NS NS NS
NOTE. Data presented as prevalence rate (%). The preoperative morbidity status was defined by cardiologists from preoperative files. Abbreviations: ITM, intrathecal morphine; CVA, cerebrovascular accident; PVD, peripheral vascular disease.
reversed, sustained (ⱖ5 seconds) head lift or tongue protrusion, maximum inspiratory pressure ⬍⫺20 cmH2O, tidal volume ⬎5 mL/kg, respiratory rate ⬍25/min, normal arterial blood gases (pH ⬎7.30, normocapnia), and PaO2/FIO2 ⬎200. When extubation was inappropriate, the double-lumen endotracheal tube was changed to a single-lumen tube using an intravenous bolus of propofol, 1 mg/kg body weight. After the surgery was completed, the patients were transferred to the postanesthesia care unit and later to the intermediate cardiac surgery unit. Postoperative pain was treated with intermittent doses (3 mg) of intravenous morphine when the patient showed signs of pain including hypertension, tachycardia, and agitation without any signs of cardiovascular compromise. The medical staff caring for the patients postoperatively was not aware of the intraoperative anesthetic management. The following data were recorded: demographics, preoperative morbidity status, patient’s temperature during the surgery, coronary artery occlusion and anastomosis time, the time passed from the end of the procedure to extubation, bleeding from the chest tube in first 24 hours, rate of reintubation, use of intravenous morphine in first 24 postoperative hours, opiates’ side effects like pruritus, nausea and vomiting, and length of hospitalization. Preoperative morbidity status was analyzed using a Fisher exact test. A Mann-Whitney U test was performed for comparison of the intraand postoperative data between the 2 groups. A p value less than 0.05 was considered statistically significant. Mean ⫾ SD and median are presented for continuous variables. RESULTS
Patients in both groups were comparable for age, sex, weight, and preoperative morbidity (Table 1). Twenty patients
were treated with atenolol, 18 with isosorbide-5-mononitrate, and 5 with enalapril. Four patients in the ITM group and none in the control group were extubated in the operating room. Time elapsed until postsurgery extubation was 3.1 ⫾ 4.7 hours in the ITM group and 6.3 ⫾ 3.4 hours in the control group (p ⫽ 0.02) (median 1 and 5 hours, respectively). No reintubations took place in either group. The intraoperative dose of fentanyl was 0.55 ⫾ 0.2 mg in the ITM group and 1.1 ⫾ 0.2 mg in the control group (p ⬍ 0.0001, median 0.5 and 1.0 mg, respectively) (Table 2). Postoperatively, the ITM group patients received significantly less intravenous morphine than did the control group (2.0 ⫾ 3.5 mg v 16.1 ⫾ 4.8 mg, respectively; p ⬍ 0.0001; median 0.0 and 10 mg, respectively) (Table 3). There were no differences in left anterior descending artery ischemic time, in duration of the surgical procedure, in intraoperative fluid requirements, or in mean postoperative blood loss (Table 2). Hospitalization period was shorter in the ITM group (3.9 ⫾ 1.7 days compared with the control group 4.9 ⫾ 1.4 days, p ⫽ 0.047; median 3 and 5 days, respectively) (Table 3). There were no conversions to conventional coronary artery bypass graft surgery, no postoperative myocardial infarction as defined by electrocardiogram changes and elevation of troponin I, and no postoperative focal or general neurological deficits (mono- or hemiparesis or plegia, changes in consciousness) were observed. DISCUSSION
The results of this pilot study show that implementation of ITM injection in MIDCAB surgery decreases the amount of opiates required both intra- and postoperatively and shortens the time until extubation, thus making a fast-track policy easier to apply. The authors found intrathecal morphine injection an effective method to control postthoracotomy pain, and it seems that administration of ITM might shorten the hospital length of stay in MIDCAB patients. To cope with postoperative pain and apply fast-track surgery, several types of regional anesthesia have been used in conventional cardiac surgery as well as off-bypass cardiac surgery. These include intrathecal anesthesia with morphine sulphate or bupivacaine,8-12,15 thoracic epidural analgesia,13,14 and intrapleural analgesia.14 MIDCAB incorporates important aspects of thoracic surgery. Unlike conventional cardiac surgery, anterior thoracotomy is associated with costal trauma causing severe postoperative pain. To achieve one-lung ventilation, a double-lumen endobronchial tube is used. The authors prefer this tube because it allows better management of the collapsed lung in terms of
Table 2. Intraoperative Parameters Parameter\Group
Length of surgery (min) Temperature at the end of the surgery (°C) Fentanyl (mg) Intravenous fluid requirement (mL) LAD ischemic time (min)
Control
168 ⫾ 42 (154) 34.8 ⫾ 0.5 (34.9) 1.1 ⫾ 0.2 (1.1) 2300 ⫾ 554 (2500) 11.1 ⫾ 2.5 (11.0)
NOTE. Data presented as mean ⫾ SD (median). Abbreviations: LAD, left anterior descending artery; ITM, intrathecal morphine.
ITM
162 ⫾ 30 (16) 34.9 ⫾ 0.5 (34.8) 0.55 ⫾ 0.2 (0.5) 1927 ⫾ 341 (1940) 11.6 ⫾ 2.0 (11.0)
p Value
NS NS ⬍0.0001 NS NS
42
ZISMAN ET AL
Table 3. Postoperative Characteristics Parameter\Group
Control
ITM
p Value
Morphine requirements in the first 24 postoperative hours (mg) Chest tube bleeding in first 24 postoperative hours (mL) Extubation time (h) Range (h) Hospital length of stay (d)
16.1 ⫾ 4.8 (10) 449 ⫾ 194 (485) 6.32 ⫾ 3.4 2-12 (5) 4.9 ⫾ 1.4 (5)
2.0 ⫾ 3.5 (0) 470 ⫾ 151 (410) 3.18 ⫾ 4.7 0-11 (1) 3.9 ⫾ 1.7 (3)
⬍0.0001 NS 0.016 0.047
NOTE. Data presented as mean ⫾ SD (median). Abbreviation: ITM, intrathecal morphine.
oxygen supply, suctioning, and application of positive endexpiratory pressure if needed. This has to be exchanged for an endotracheal tube at the end of the procedure if the patient remains ventilated. Reintubation at the end of the surgery entails potential risk and could lead to unnecessary complications. It is common therefore to combine general anesthesia with thoracic epidural block for thoracic surgery. In the case of MIDCAB, thoracic epidural analgesia may have additional benefits in terms of implementation of fast-track policy, but its sometimes undesirable hemodynamic effects and the associated increased incidence (even compared with spinal injection) of epidural or spinal hematomas, especially in patients exposed to heparinization, precluded the authors from using it.16 ITM sulfate, which has a long-lasting analgesic effect, was initially given to patients undergoing conventional cardiac surgery by Mathews and Abrams in 1980.6 Since then, several studies investigated the influence of intrathecal morphine on patients having cardiac surgery.8-11,15,17 The prospective randomized controlled studies8-10,17 showed decreased need for postoperative analgesics in patients who received ITM, but in contrast to the authors’ results, found no differences in extubation time probably because of the usual protocol for premedication and intraoperative opiate dose. Earlier extubation in the ITM patient group could be explained by the following adjusted anesthesia protocol: light premedication, delay of painful stimuli for 35 to 40 minutes after intrathecal injection, and significantly smaller intraoperative doses of fentanyl. Most of the patients in the ITM group received only an induction dose of fentanyl (5-7 g/kg), and there was no need for additional narcotics during the surgery. The authors believe that the combination of a single-induction dose of fentanyl with intrathecal morphine led to a shorter extubation time and allowed the authors to extubate 4 patients in the ITM group immediately after surgery. The extended effect of ITM was prominent during the first 24 hours after the surgery and was shown by the significantly reduced need for analgesic medications. Intrathecal injection, especially in the presence of anticoagulation, entails the risk of epidural hematoma. The precise
incidence of subarachnoid or epidural hematoma in patients after spinal injection is not known but is estimated at 0.8: 10,000.18 Although very rare, subarachnoid or epidural hematoma occurred in patients who underwent lumbar puncture followed by systemic heparinization.19 The maximal risk of occurrence of epidural hematoma in cardiac surgery with cardiopulmonary bypass is estimated at 1:1,500.16 In MIDCAB surgery, the maximal combined risk of conversion to conventional coronary artery bypass graft and epidural hematoma was estimated to be less than 1:30,000.20 To the best of the authors’ knowledge, no hematoma formation was observed so far in several studies evaluating the use of spinal injection in cardiac surgery.8-10,17 This study excluded patients with an abnormal coagulation profile and those in whom 2 attempts at intrathecal injection failed to lower the risk of an epidural hematoma. No neurologic complications were observed in any of the patients. A main factor that probably limited the early recovery from anesthesia in both groups was hypothermia at the end of the surgery. Even though the authors attempted to prevent hypothermia by the use of a warm operating room, heated fluids and forced warm air, both groups of patients suffered from hypothermia at the end of surgery. Although in the present study the intrathecal morphine group had significantly shorter postoperative hospitalization time, caution is advised in interpretation of these results. These results may reflect the small study group and the retrospective design of the study. In conclusion, the authors found that intrathecal morphine was effective in decreasing the narcotics requirement during surgery and the immediate postoperative period. The use of intrathecal morphine allowed for earlier extubation (in some patients even in the operating room), which accelerated postoperative recovery. Because of the small size of the study and its retrospective character, there is a need for a larger controlled randomized study before intrathecal morphine can be recommended for routine use in MIDCAB. ACKNOWLEDGMENT The authors thank Dr Ada Tamir for her help with statistical analysis.
REFERENCES 1. Juneja R, Metha Y, Mishra Y, et al: Minimally invasive coronary artery surgery: anesthetic considerations. J Cardiothorac Vasc Anesth 11:123-124, 1997 2. Maslow AD, Park KW, Pawlowski J, et al: Minimally invasive direct coronary artery bypass grafting: Changes in anesthetic management and surgical procedure. J Cardiothorac Vasc Anesth 13:417-423, 1999
3. London MJ, Shroyer ALW, Jernigan B, et al: Fast-track cardiac surgery in a department of Veterans Affairs patient population. Ann Thorac Surg 64:134-41, 1997 4. 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 85:1300-1310, 1996
THE EFFECTS OF INTRATHECAL MORPHINE
5. Swenson JD, Hullander RM, Wingler K, et al: Early extubation after cardiac surgery using combined intrathecal sufentanil and morphine. J Cardiothorac Vasc Anesth 8:509-514, 1994 6. Mathews ET, Abrams LD: Intrathecal morphine in open-heart patients. Lancet 2:543, 1980 7. Stoelting RK: Intrathecal morphine, an underused combination for postoperative pain management. Anesth Ann 687:707-709, 1989 8. Alhashemi JA, Sharpe MD, Harris CL, et al: Effect of subarachnoid morphine administration on extubation time following coronary artery bypass grafting. J Cardiothorac Vasc Anesth 14:639-644, 2000 9. Chaney MA, Furry PA, Fluder EM, et al: Intrathecal morphine for coronary artery bypass grafting and early extubation. Anesth Analg 84:241-248, 1997 10. Chaney MA, Nikolov MP, Blakeman BP, et al: Intrathecal morphine for coronary artery graft procedure and early extubation revisited. Cardiothorac Vasc Anesth 13:574-578, 1999 11. Bettex DA, Schmidlin D, Chassot PG, et al: Intrathecal sufentanil-morphine shortens the duration of intubation and improves analgesia in fast-track cardiac surgery. Can J Anesth 49:711-717, 2002 12. Heres EK, Marquez J, Malkowski MJ, et al: MIDCAB: Anesthetic, monitoring, and pain control considerations. J Cardiothorac Vasc Anesth 12:385-389, 1998 13. Kirnö K, Friberg P, Grzegorczyk A, et al: Thoracic epidural anesthesia during coronary artery bypass surgery: Effects on cardiac
43
sympathetic activity, myocardial blood flow and metabolism, and central hemodynamics. Anesth Analg 79:1075-1081, 1994 14. Metha Y, Swaminathan M, Mishra Y, et al: A comparative evaluation of intrapleural and thoracic epidural analgesia for postoperative pain relief after minimally invasive direct coronary artery bypass surgery. J Cardiothorac Vasc Anesth 12:162-165, 1998 15. Kowalewski RJ, MacAdams CL, Eagle CJ, et al: Anaesthesia for coronary artery bypass surgery supplemented with subarachnoid bupivacaine and morphine: A report of 18 cases. Can J Anesth 41:11891195, 1994 16. Ho AMH, Chung DC, Joynt GM: Neuraxial blockade and hematoma in cardiac surgery. Chest 117:551-555, 2000 17. Vanstrum GS, Bjornson KM, Ilko R: Postoperative effects of intrathecal morphine in coronary artery bypass surgery. Anesth Analg 67:261-267, 1988 18. Auroy Y, Benhamou D, Bargues L, et al: Major complications of regional anesthesia in France. Anesthesiology 97:1274-1280, 2002 19. Brem SS, Hafler DA, Van Uitert RL, et al: Spinal subarachnoid hematoma. A hazard of lumbar puncture resulting in reversible paraplegia. N Engl J Med 304:1020-1021, 1981 20. De Vries AJ, Mariani MA, van der Maaten JMAA, et al: To ventilate or not after minimally invasive direct coronary bypass surgery: The role of epidural anesthesia. J Cardiothorac Vasc Anesth 16:21-26, 2002
0.016). Morphine requirements in 24 hours after surgery were 2.0 ⴞ 3.5 mg in the ITM and 16.1 ⴞ 4.8 mg in the control group (p < 0.0001). There were no differences in ischemic time, intraoperative fluid requirements, postoperative blood loss, and duration of surgical procedure. Hospital length of stay was shorter in the ITM group compared with the control group (3.9 ⴞ 1.7 days v 4.9 ⴞ 1.4 days, respectively, p ⴝ 0.047). Conclusions: ITM has to be considered in MIDCAB surgery as an effective component of the perioperative analgesia. The safety and effects of ITM in the patient’s recovery after MIDCAB surgery should be evaluated in further prospective studies. © 2005 Elsevier Inc. All rights reserved.
M
to the general anesthesia comprised the study group. They received 7 g/kg of preservative-free morphine sulfate before the induction of anesthesia. The control group consisted of 11 patients with a similar medical condition who did not consent to receive an intrathecal injection of morphine or when 2 attempts to perform spinal injection failed. For patients to be eligible to receive ITM (or to be included as controls) the following criteria were used: good left ventricular function (ejection fraction ⬎40%), no evidence of chronic obstructive pulmonary disease, normal coagulation profile (prothrombin time, partial thromboplastin time, fibrinogen, platelet count ⬎100,000/mL3), no history of abnormal bleeding, no intake of anticoagulation or antiplatelet medications besides aspirin, no abnormal lumbar spine anatomy or serious neurologic pathology, and primary coronary artery surgery (single grafting) without use of inotropic drugs or intra-aortic balloon pump before surgery. Patients in both groups were premedicated with oral oxazepam, 10 mg. Monitoring included 2-lead electrocardiogram with ST-analyzer, invasive blood pressure, central venous pressure, oral and rectal temperature, pulse oximetry, arterial blood gases, capnography, and urinary output. The patients in the ITM group received an intrathecal injection of 7 g/kg of preservative-free morphine sulfate through a spinal pencil-point 24-g needle before induction of general anesthesia. Only 2 attempts of intrathecal injection were permitted. If the spinal tap appeared bloody or the first 2 attempts failed, surgery proceeded with general anesthesia alone. Induction of anesthesia was the same in both groups and consisted of midazolam, fentanyl, propofol, succinylcholine, and insertion of a double-lumen endobronchial tube for separation of the lungs. Maintenance of anesthesia was performed using intravenous fentanyl (total dose up to 10 g/kg), midazolam (total dose up to 5 mg), pancuronium bromide (0.01mg/kg), and isoflurane as needed. An additional aliquot of fentanyl was given when no change was made in the dosage of hypnotics or isoflurane and the signs of pain appeared including increases in blood pressure and heart rate and tears. Particular efforts were made to keep the body temperature above 35°C during the surgery. Anticoagulation was achieved by injecting 100 U/kg of heparin. If the targeted activated coagulation time (300 seconds) was not reached, additional heparin was given. After the left anterior descending artery anastomosis was performed, protamine sulfate at a dose of 0.5 mg/kg was given to normalize the activated coagulation time below 170 seconds. At the end of the surgery, an attempt to extubate the patient in the operating room was performed according to the following criteria: the patient is nearly fully awake, muscle relaxants have been
INIMALLY INVASIVE direct coronary artery bypass surgery (MIDCAB) performed through a left thoracotomy has been suggested either for patients with 1-vessel coronary disease or for patients who are scheduled for a combined surgical and endovascular revascularization procedure. Although MIDCAB is a shorter and less extended procedure than conventional cardiac surgery, left thoracotomy, through which it is performed, is associated with costal trauma leading to significant postoperative pain.1,2 Effective perioperative pain control in patients undergoing MIDCAB is crucial during recovery and for application of a fast-track pathway.3-5 Intrathecal morphine administration is effective in controlling postoperative pain and has been used in cardiac surgery since 1980, despite the potential risk of dural puncture.6 Because of its lipophilic characteristic, morphine sulphate injected intrathecally, even at the lumbar level, produces widespread, effective analgesia.7 Spinal injection of opiates was shown to be more effective in postoperative pain control than the standard technique, but faster recovery was not observed.5,8-10 In this study, the authors compared the outcome of MIDCAB patients who received intrathecal morphine as an adjuvant to general anesthesia with those who received solely general anesthesia. METHODS Twenty-two consecutive patients scheduled for elective MIDCAB surgery took part in this retrospective cohort study. After detailed explanation about the neurologic risks of intrathecal injection, 11 patients who agreed to receive intrathecal morphine (ITM) in addition
From the Departments of *Anesthesiology and Critical Care Medicine and †Cardiothoracic Surgery, Carmel Lady Davis Medical Center, Haifa, Israel. Address reprint requests to Eliyahu Zisman, MD, Department of Anesthesiology and Critical Care Medicine, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel. E-mail: [email protected] © 2005 Elsevier Inc. All rights reserved. 1053-0770/05/1901-0007$30.00/0 doi:10.1053/j.jvca.2004.11.007 40
KEY WORDS: coronary artery surgery, MIDCAB, thoracotomy, intrathecal morphine, perioperative pain control
Journal of Cardiothoracic and Vascular Anesthesia, Vol 19, No 1 (February), 2005: pp 40-43
THE EFFECTS OF INTRATHECAL MORPHINE
41
Table 1. Demographic Data and Preoperative Morbidity Parameter
Control Group (n ⫽ 11)
ITM Group (n ⫽ 11)
p Value
Age (y) Weight (kg) Sex; male:female Myocardial infarction Hypertension Hyperlipidemia Renal failure CVA PVD Smoking Chronic atrial fibrillation
64.7 ⫾ 13.1 86.2 ⫾ 18.8 9:2 6 (55%) 11 (100%) 6 (55%) 2 (18%) 0 (0%) 1 (9%) 4 (36%) 0 (0%)
63.4 ⫾ 15.0 73.55 ⫾ 11.7 9:2 4 (36%) 5 (45%) 6 (55%) 2 (18%) 1 (9%) 1 (9%) 3 (27%) 1 (9%)
NS NS NS NS 0.012 NS NS NS NS NS NS
NOTE. Data presented as prevalence rate (%). The preoperative morbidity status was defined by cardiologists from preoperative files. Abbreviations: ITM, intrathecal morphine; CVA, cerebrovascular accident; PVD, peripheral vascular disease.
reversed, sustained (ⱖ5 seconds) head lift or tongue protrusion, maximum inspiratory pressure ⬍⫺20 cmH2O, tidal volume ⬎5 mL/kg, respiratory rate ⬍25/min, normal arterial blood gases (pH ⬎7.30, normocapnia), and PaO2/FIO2 ⬎200. When extubation was inappropriate, the double-lumen endotracheal tube was changed to a single-lumen tube using an intravenous bolus of propofol, 1 mg/kg body weight. After the surgery was completed, the patients were transferred to the postanesthesia care unit and later to the intermediate cardiac surgery unit. Postoperative pain was treated with intermittent doses (3 mg) of intravenous morphine when the patient showed signs of pain including hypertension, tachycardia, and agitation without any signs of cardiovascular compromise. The medical staff caring for the patients postoperatively was not aware of the intraoperative anesthetic management. The following data were recorded: demographics, preoperative morbidity status, patient’s temperature during the surgery, coronary artery occlusion and anastomosis time, the time passed from the end of the procedure to extubation, bleeding from the chest tube in first 24 hours, rate of reintubation, use of intravenous morphine in first 24 postoperative hours, opiates’ side effects like pruritus, nausea and vomiting, and length of hospitalization. Preoperative morbidity status was analyzed using a Fisher exact test. A Mann-Whitney U test was performed for comparison of the intraand postoperative data between the 2 groups. A p value less than 0.05 was considered statistically significant. Mean ⫾ SD and median are presented for continuous variables. RESULTS
Patients in both groups were comparable for age, sex, weight, and preoperative morbidity (Table 1). Twenty patients
were treated with atenolol, 18 with isosorbide-5-mononitrate, and 5 with enalapril. Four patients in the ITM group and none in the control group were extubated in the operating room. Time elapsed until postsurgery extubation was 3.1 ⫾ 4.7 hours in the ITM group and 6.3 ⫾ 3.4 hours in the control group (p ⫽ 0.02) (median 1 and 5 hours, respectively). No reintubations took place in either group. The intraoperative dose of fentanyl was 0.55 ⫾ 0.2 mg in the ITM group and 1.1 ⫾ 0.2 mg in the control group (p ⬍ 0.0001, median 0.5 and 1.0 mg, respectively) (Table 2). Postoperatively, the ITM group patients received significantly less intravenous morphine than did the control group (2.0 ⫾ 3.5 mg v 16.1 ⫾ 4.8 mg, respectively; p ⬍ 0.0001; median 0.0 and 10 mg, respectively) (Table 3). There were no differences in left anterior descending artery ischemic time, in duration of the surgical procedure, in intraoperative fluid requirements, or in mean postoperative blood loss (Table 2). Hospitalization period was shorter in the ITM group (3.9 ⫾ 1.7 days compared with the control group 4.9 ⫾ 1.4 days, p ⫽ 0.047; median 3 and 5 days, respectively) (Table 3). There were no conversions to conventional coronary artery bypass graft surgery, no postoperative myocardial infarction as defined by electrocardiogram changes and elevation of troponin I, and no postoperative focal or general neurological deficits (mono- or hemiparesis or plegia, changes in consciousness) were observed. DISCUSSION
The results of this pilot study show that implementation of ITM injection in MIDCAB surgery decreases the amount of opiates required both intra- and postoperatively and shortens the time until extubation, thus making a fast-track policy easier to apply. The authors found intrathecal morphine injection an effective method to control postthoracotomy pain, and it seems that administration of ITM might shorten the hospital length of stay in MIDCAB patients. To cope with postoperative pain and apply fast-track surgery, several types of regional anesthesia have been used in conventional cardiac surgery as well as off-bypass cardiac surgery. These include intrathecal anesthesia with morphine sulphate or bupivacaine,8-12,15 thoracic epidural analgesia,13,14 and intrapleural analgesia.14 MIDCAB incorporates important aspects of thoracic surgery. Unlike conventional cardiac surgery, anterior thoracotomy is associated with costal trauma causing severe postoperative pain. To achieve one-lung ventilation, a double-lumen endobronchial tube is used. The authors prefer this tube because it allows better management of the collapsed lung in terms of
Table 2. Intraoperative Parameters Parameter\Group
Length of surgery (min) Temperature at the end of the surgery (°C) Fentanyl (mg) Intravenous fluid requirement (mL) LAD ischemic time (min)
Control
168 ⫾ 42 (154) 34.8 ⫾ 0.5 (34.9) 1.1 ⫾ 0.2 (1.1) 2300 ⫾ 554 (2500) 11.1 ⫾ 2.5 (11.0)
NOTE. Data presented as mean ⫾ SD (median). Abbreviations: LAD, left anterior descending artery; ITM, intrathecal morphine.
ITM
162 ⫾ 30 (16) 34.9 ⫾ 0.5 (34.8) 0.55 ⫾ 0.2 (0.5) 1927 ⫾ 341 (1940) 11.6 ⫾ 2.0 (11.0)
p Value
NS NS ⬍0.0001 NS NS
42
ZISMAN ET AL
Table 3. Postoperative Characteristics Parameter\Group
Control
ITM
p Value
Morphine requirements in the first 24 postoperative hours (mg) Chest tube bleeding in first 24 postoperative hours (mL) Extubation time (h) Range (h) Hospital length of stay (d)
16.1 ⫾ 4.8 (10) 449 ⫾ 194 (485) 6.32 ⫾ 3.4 2-12 (5) 4.9 ⫾ 1.4 (5)
2.0 ⫾ 3.5 (0) 470 ⫾ 151 (410) 3.18 ⫾ 4.7 0-11 (1) 3.9 ⫾ 1.7 (3)
⬍0.0001 NS 0.016 0.047
NOTE. Data presented as mean ⫾ SD (median). Abbreviation: ITM, intrathecal morphine.
oxygen supply, suctioning, and application of positive endexpiratory pressure if needed. This has to be exchanged for an endotracheal tube at the end of the procedure if the patient remains ventilated. Reintubation at the end of the surgery entails potential risk and could lead to unnecessary complications. It is common therefore to combine general anesthesia with thoracic epidural block for thoracic surgery. In the case of MIDCAB, thoracic epidural analgesia may have additional benefits in terms of implementation of fast-track policy, but its sometimes undesirable hemodynamic effects and the associated increased incidence (even compared with spinal injection) of epidural or spinal hematomas, especially in patients exposed to heparinization, precluded the authors from using it.16 ITM sulfate, which has a long-lasting analgesic effect, was initially given to patients undergoing conventional cardiac surgery by Mathews and Abrams in 1980.6 Since then, several studies investigated the influence of intrathecal morphine on patients having cardiac surgery.8-11,15,17 The prospective randomized controlled studies8-10,17 showed decreased need for postoperative analgesics in patients who received ITM, but in contrast to the authors’ results, found no differences in extubation time probably because of the usual protocol for premedication and intraoperative opiate dose. Earlier extubation in the ITM patient group could be explained by the following adjusted anesthesia protocol: light premedication, delay of painful stimuli for 35 to 40 minutes after intrathecal injection, and significantly smaller intraoperative doses of fentanyl. Most of the patients in the ITM group received only an induction dose of fentanyl (5-7 g/kg), and there was no need for additional narcotics during the surgery. The authors believe that the combination of a single-induction dose of fentanyl with intrathecal morphine led to a shorter extubation time and allowed the authors to extubate 4 patients in the ITM group immediately after surgery. The extended effect of ITM was prominent during the first 24 hours after the surgery and was shown by the significantly reduced need for analgesic medications. Intrathecal injection, especially in the presence of anticoagulation, entails the risk of epidural hematoma. The precise
incidence of subarachnoid or epidural hematoma in patients after spinal injection is not known but is estimated at 0.8: 10,000.18 Although very rare, subarachnoid or epidural hematoma occurred in patients who underwent lumbar puncture followed by systemic heparinization.19 The maximal risk of occurrence of epidural hematoma in cardiac surgery with cardiopulmonary bypass is estimated at 1:1,500.16 In MIDCAB surgery, the maximal combined risk of conversion to conventional coronary artery bypass graft and epidural hematoma was estimated to be less than 1:30,000.20 To the best of the authors’ knowledge, no hematoma formation was observed so far in several studies evaluating the use of spinal injection in cardiac surgery.8-10,17 This study excluded patients with an abnormal coagulation profile and those in whom 2 attempts at intrathecal injection failed to lower the risk of an epidural hematoma. No neurologic complications were observed in any of the patients. A main factor that probably limited the early recovery from anesthesia in both groups was hypothermia at the end of the surgery. Even though the authors attempted to prevent hypothermia by the use of a warm operating room, heated fluids and forced warm air, both groups of patients suffered from hypothermia at the end of surgery. Although in the present study the intrathecal morphine group had significantly shorter postoperative hospitalization time, caution is advised in interpretation of these results. These results may reflect the small study group and the retrospective design of the study. In conclusion, the authors found that intrathecal morphine was effective in decreasing the narcotics requirement during surgery and the immediate postoperative period. The use of intrathecal morphine allowed for earlier extubation (in some patients even in the operating room), which accelerated postoperative recovery. Because of the small size of the study and its retrospective character, there is a need for a larger controlled randomized study before intrathecal morphine can be recommended for routine use in MIDCAB. ACKNOWLEDGMENT The authors thank Dr Ada Tamir for her help with statistical analysis.
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THE EFFECTS OF INTRATHECAL MORPHINE
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