Morphine With Adjuvant Ketamine vs Higher Dose of Morphine Alone for Immediate Postthoracotomy Analgesia

doi:10.1378/chest.08-0246

Chest

Volume 136, Issue 1, July 2009, Pages 245-252

https://doi.org/10.1378/chest.08-0246 Get rights and content

Background

Thoracotomy is associated with severe pain. We hypothesized that the concomitant use of a subanesthetic dose of ketamine plus a two-third-standard morphine dose might provide more effective analgesia with fewer side effects than a standard morphine dose for early pain control.

Methods

We conducted a 6-month randomized, double-blind study in patients undergoing thoracotomy for minimally invasive direct coronary artery bypass or for lung tumor resection. After extubation, when objectively awake (≥ 5/10 visual analogue scale [VAS]) and complaining of pain (≥ 5/10 VAS), patients were connected to patient-controlled IV analgesia delivering 1.5 mg of morphine plus saline solution (MO) or 1.0 mg of morphine plus a 5-mg ketamine bolus (MK), with a 7-min lockout time. Rescue IM diclofenac, 75 mg, was available. Follow-up lasted 4 h.

Results

Forty-one patients completed the study. MO patients (n = 20) used 6.8 ± 1.9 mg/h (mean ± SD) and 5.5 ± 3.6 mg/h of morphine during the first and second hours, respectively; MK patients (n = 21) used 3.7 ± 1.2 mg/h and 2.8 ± 2.3 mg/h, respectively (p < 0.01). The 4-h activation rate of the device was double in the MO patients than in the MK patients (66 ± 54 vs 28 ± 20, p < 0.001). The maximal self-rated pain score was 5.6 ± 1.0 for the MO group vs 3.7 ± 0.7 for the MK group (p < 0.01). Four MO patients vs one MK patient required diclofenac; 6 MO patients but no MK patients had oxygen saturation by pulse oximetry < 94% on a fraction of inspired oxygen of 0.4 (p < 0.01); two MO patients required reintubation. Paco₂ was higher in the MO group (40 ± 6 mm Hg vs 33 ± 5 mm Hg, p < 0.05). Heart rate, BP, and incidence of nausea/vomiting were similar; no ketamine-related hallucinations were detected.

Conclusions

Subanesthetic ketamine combined with a 35%-lower morphine dose provided equivalent pain control compared to the standard morphine dose alone, with fewer adverse side effects and a 45% reduction in morphine consumption.

Trial registration

ClinicalTrials.gov Identifier: NCT00625911

Section snippets

Materials and Methods

This study is one part of a larger study conducted in the Post Anesthesia Care Unit on patients from the Department of Cardiovascular and Thoracic Surgery at the Tel-Aviv Sourasky Medical Center during the period 2001–2004 and had been approved by the Ethics Committee of the institution. The present cohort consisted of the first, more homogeneous group of patients, whereas data pertaining to the second and larger part of the cohort appear in a recent report elsewhere.²² Forty-four patients

Results

Of 62 screened patients, 44 patients fulfilled the study criteria for randomization. Three patients subsequently dropped out after surgery because they required continuous ventilation (CONSORT statement, Fig 1); no MIDCAB patient was converted to an on-pump procedure. Demographic, anesthesia, and surgical data were similar between the two drug study groups (Table 1); intraoperative blood replacement and fluid infusion were similar as well (data not shown). Baseline (immediately before starting

Discussion

Our study demonstrates that the administration of an IV subanesthetic dose (5 mg/bolus) of ketamine combined with two thirds of the standard (1.5-mg) morphine dose provided lower subjective measures of pain (by > 2 points on a scale of 1 to 10) than the standard morphine dose alone during the immediate (4 h) postthoracotomy period. The combined protocol was also associated with remarkably stable hemodynamic conditions and better respiratory parameters than the MO group. These objective effects

Acknowledgment

The authors thank Esther Eshkol, MA (institutional medical copyeditor, Tel Aviv Sourasky Medical Center) for editorial assistance, and the nursing staff of the PACU for their collaboration and dedication.

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The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with psychodysleptic, hallucinogenic and dissociative properties. Following the first administration of ketamine to humans in 1964 in Jackson prison (Michigan, USA), its dissociative effects associated with short anaesthesia were reported, and a patent for its human use was filed in 1966. In the 1990s, the discovery of opioid-induced hyperalgesia sparked interest in ketamine as an analgesic. In recent years, the human use of ketamine, and in particular its esketamine enantiomer, has shifted towards the treatment of depression. The first cases of ketamine abuse were reported in 1992 in France, leading to special surveillance by the health authorities, and its inclusion in the list of narcotic drugs in 1997. Today, ketamine has become an attractive substance for recreational use, gradually emerging from alternative techno circles to spread to more commercial party scenes. These elements represent a public health concern, associated with the risk of developing new chemically synthesized analogues, the harmful effects of which are still little known.
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Postoperative hyperalgesia (POH) is a condition characterized by signs and symptoms of pain despite the provision of conventional analgesia. In most cases, anesthesiologists are called upon soon after surgery, but occasionally it may occur as a late event. Persistent uncontrolled pain may transform into chronic or neuropathic pain. Correct diagnosis of POH is essential since similar phenomenon may exacerbate if misdiagnosed, while proper treatment is frequently achievable by pharmacological remedies.
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Parts of this study were presented at the Euroanaesthesia 2003 Meeting, Glasgow, Scotland May 31-June 3, 2003; and at the fifth International Congress on Coronary Artery Disease, Florence, Italy, October 19–22, 2003.

No financial support was received for this clinical trial.

The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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Chest

Original ResearchThoracic surgeryMorphine With Adjuvant Ketamine vs Higher Dose of Morphine Alone for Immediate Postthoracotomy Analgesia

Background

Methods

Results

Conclusions

Trial registration

Section snippets

Materials and Methods

Results

Discussion

Acknowledgment

J Cardiothorac Vasc Anesth

Ann Thorac Surg

J PeriAnesth Nurs

Pain

Pain

Pain

Pain

Ann Emerg Med

J Thorac Cardiovasc Surg

Heart Lung

Pharmacol Res

J Cardiothorac Vasc Anesth

A prospective series, Ann Emerg Med

Analgesic pharmacology: II. Specific analgesics

J Am Acad Orthop Surg

A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery

Anesth Analg

The effects of postoperative pain management on immune response to surgery

Anesth Analg

Original Research
Thoracic surgery
Morphine With Adjuvant Ketamine vs Higher Dose of Morphine Alone for Immediate Postthoracotomy Analgesia