Efficacy of Small Doses of Ketamine With Morphine to Decrease Procedural Pain Responses During Open Wound Care Carmen Mabel Arroyo-Novoa, RN, PhD,* Milagros I. Figueroa-Ramos, RN, PhD,* Christine Miaskowski, RN, PhD,w Geraldine Padilla, PhD,w Steven M. Paul, PhD,w Pablo Rodrı´guez-Ortiz, MD,z Nancy A. Stotts, RN, EdD,w and Kathleen A. Puntillo, RN, DNScw Objective: The purpose of this study was to evaluate differences in pain intensity, pain quality, physiological measures, and adverse effects when patients received morphine with saline (MS) compared with morphine and a small dose of ketamine (MK) before an open wound care procedure (WCP). Methods: A randomized, cross-over design was used to determine whether the addition of a small dose of ketamine would potentiate morphine’s analgesic effects and decrease WCP pain intensity. Patients were randomized to receive either 0.1 mg/kg of morphine (8 mg maximum) plus saline intravenously (IV) or 0.05 mg/kg of morphine (4 mg maximum) plus ketamine 0.25 mg/kg IV before the WCP. Patients were crossed-over to receive the alternate treatment during the next WCP. Results: Eleven male patients participated in the study. Mean rank of pain intensity during WCP-MK was significantly less than during WCP-MS (P=0.005). Mean±standard error of mean pain intensity during the WCP-MK was 3.09±0.99, whereas it was 6.82±0.92 during the WCP-MS. However, 91% of the patients had adverse effects (eg, strange sensations, hallucinations, blurred vision) with MK versus 0% with MS. Diastolic blood pressure was significantly higher during the WCP-MK. Discussion: Ketamine with morphine significantly reduced proce- dural wound pain intensity during WCP. Adverse effects and higher diastolic BP occurred with MK. Further research is warranted to determine the optimal analgesic dose of ketamine or if the addition of a benzodiazepine would mitigate the psychotomimetic effects of ketamine. Key Words: wound care, procedural pain, ketamine, morphine, hyperalgesia (Clin J Pain 2011;27:561–566) M any patients in critical and acute care settings have open wounds as a result of trauma or surgery. These patients undergo wound care procedures (WCPs) to promote wound healing and prevent infection. However, WCPs are associated with a significant amount of pain intensity. 1,2 Although it is known that open wounds are painful, the mechanisms involved in wound pain are not well under- stood. 3 Injury to superficial or deep tissues may provoke an inflammatory response that induces the release of chemical mediators. When peripheral neurons are activated, dorsal horn neurons are sensitized by the release of transmitters from peripheral nociceptors. This process can result in central sensitization that leads to an increase in pain transmission. 4,5 As a result, uninjured areas around the site of injury become hyperalgesic (ie, secondary hyperalgesia occurs). 6 N-methyl-D-aspartate (NMDA) glutamate recep- tors participate in the process of central sensitization of dorsal horn neurons. 7 Although the contribution of hyperalgesia to post- operative pain is not well established, it is thought that hyperalgesia may increase pain intensity. 8 Ketamine is an NMDA antagonist, that has antihyperalgesic and analgesic properties at small doses. In patients who underwent a nephrectomy, small doses of ketamine reduced the area of secondary hyperalgesia around the surgical incision. 9 Several studies have evaluated the effects of low doses of intravenous (IV) ketamine with opioid analgesics for the management of postoperative pain. Two studies found that ketamine administered at the end of surgery (ie, hysterec- tomy, laparoscopic cholecystectomy) resulted in signifi- cantly lower postoperative pain intensity scores than if ketamine or saline was administered before the surgical incision. 10,11 In another study that evaluated the effect of a single dose of ketamine on pain intensity in postoperative patients who had morphine-resistant pain (ie, pain that did not resolve with morphine 0.1 mg/kg within a 30 min period) in the recovery room, 12 overall pain intensity was significantly lower in the morphine plus ketamine group (MK; P<0.001) compared with the morphine plus saline group (MS). In addition, an immediate (ie, <10 min) and significant decrease in pain intensity was found among these patients. In contrast, no differences in postoperative pain inten- sity scores were found in patients who received ketamine at the end of an arthroscopic anterior ligament repair surgical procedure compared with those who received saline. 13 In another study, 14 MK compared with MS did not produce an analgesic effect in postoperative patients who had pain after receiving 2 doses of morphine in recovery room. Finally, in a study of trauma patients with severe pain, 15 small doses of ketamine and morphine compared with placebo and morphine, had no effect on pain intensity Copyright r 2011 by Lippincott Williams & Wilkins Received for publication October 3, 2010; revised January 11, 2011; accepted January 20, 2011. From the *School of Nursing; zSchool of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico; and wSchool of Nursing, University of California, San Francisco, San Francisco, CA. The authors declare no conflict of interest. Supported by a research scholarship from the Association for the Advancement of Wound Care. Mr. Carlos Tan˜o´n from Datascope, Puerto Rico, loaned the Accutorr Plus. Reprints: Carmen Mabel Arroyo-Novoa, RN, PhD, School of Nursing, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan, Puerto Rico 00936-5067 (e-mail: carmen. arroyo1@upr.edu). ORIGINAL ARTICLE Clin J Pain  Volume 27, Number 7, September 2011 www.clinicalpain.com | 561