Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects☆
Introduction
Thoracotomy, whether performed for the resection of lung tumor or for coronary revascularization either by MIDCAB or via OPCAB, is associated with severe and sometimes debilitating pain [1], [2]. Catecholamine release in response to nociceptive stimuli [3] in these patients is associated with undesirable hemodynamic consequences as well as disturbances in respiratory, endocrine, metabolic [4] and immune functions [5]. These changes may increase the rate of complications, prolong hospitalization and raise costs. Importantly, if acute pain is not effectively controlled, it may evolve into severe, chronic pain [6].
Postoperative pain that is uncontrollable despite the administration of considerable amounts of IV morphine could suggest tolerance to the drug [7], [8], [9]. The administration of large amounts of morphine to the awakening patient may cause respiratory and hemodynamic depression [10], [11]. These effects may be especially serious when they follow lung lobectomy [2] or when they occur in patients with poor left ventricular function [12], [13]. For these reasons, supplementation of morphine with non-narcotics (adjuvant agents) may be a preferred way of effectively controlling pain while reducing the incidence of adverse events [14], [15].
Ketamine, a non-competitive NMDAR antagonist, was shown to enhance opioid-induced acute antinociception [16]. It was also shown to reduce hyperalgesia, prevent opioid tolerance in animals [17] and lower morphine resistance in humans [18]. The concomitant administration of the two drugs also lowered morphine consumption both in the immediate and delayed postoperative period [19]. Given that sub-anesthetic (≤500 μg/kg) doses of ketamine rarely produce undesirable hemodynamic alterations (e.g., elevated heart rate and blood pressure) [20], we hypothesized that by combining a sub-anesthetic dose of ketamine with morphine, we could effectively control pain with less morphine and thereby minimize drowsiness with no detrimental effect upon hemodynamic stability or respiration.
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Patients and methods
After the study protocol was approved by the Ethics Committee of the Tel-Aviv Sourasky Medical Center, 60 patients scheduled for elective MIDCAB or OPCAB or for lung resection via anterolateral thoracotomy during March–September 2004 were enrolled. They all gave their informed, written consent to participate in this prospective, randomized, double blind study and were assigned to one of two groups according to their national ID number. Exclusion criteria were ASA physical class >3, emergency
Results
Sixty patients fulfilled the study criteria for randomization (Table 1). Two of them (one in each of the two groups) subsequently dropped out of the study because they required continuous ventilation. The data of another MK patient were not analyzed because the patient was brought back to the operating theater to control postoperative bleeding (CONSORT Statement, Fig. 1). The demographic, anesthesia and surgical data were similar between the study groups (Table 1), as were intraoperative blood
Comment
Our study demonstrated that the administration of 5 mg ketamine combined with 1 mg morphine per bolus of IV-PCA (MK group) controlled pain better than the “standard” 1.5 mg morphine/bolus of IV-PCA (MO group). Adjuvant ketamine spared morphine consumption by 50%, allowed for a shorter period of dependence on IV-PCA, and was associated with better respiratory parameters compared to morphine alone during the 72 h after thoracotomy. The combined protocol was also associated with remarkably stable
Acknowledgements
The authors thank the medical and nursing staff of the Cardiothoracic Surgery Department for their collaboration and dedication. Esther Eshkol, MA, is thanked for linguistic and editorial assistance.
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This study was presented in part at the Euroanaesthesia 2003 Meeting, Glasgow, Scotland and at the 20th International Congress of the Israel Society of Anesthesiologists, 2005, Tel Aviv, Israel.