Perioperative Drug Combinations

Perioperative Drug Combinations

PEP Topic 
Acute Pain
Description 

Researchers have assessed several drug combinations, administered in the preoperative and perioperative periods, in regard to management of the acute pain of patients with cancer. Drug combinations assessed include morphine + acetaminophen + ketoprofen + naproxen and acetaminophen + dexamethasone + dextromethorphan + celecoxib + gabapentin.

Effectiveness Not Established

Research Evidence Summaries

Gartner, R., Kroman, N., Callesen, T., & Kehlet, H. (2010). Multimodal prevention of pain, nausea and vomiting after breast cancer surgery. Minerva Anestesiologica, 76(10), 805–813.

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Study Purpose:

To evaluate the effect of a multidrug, opiate-sparing regimen for prevention of postoperative pain, nausea, and vomiting in patients after surgery for breast cancer

Intervention Characteristics/Basic Study Process:

For 1–2 hours preoperatively, patients received a drug combination consisting of 1g oral paracetamol, 8 mg dexamethasone, 30 mg dextromethorphan, 400 mg celecoxib, and 1200 mg gabapentin. In addition, patients who were anxious received 0.125 mg triazolam on request. All patients received the same anesthesia regimen. In the postanesthesia care unit (PACU), immediately after surgery, symptoms were recorded at 15-minute intervals for 12 hours. Patients who had moderate to severe pain with mobilization received 0.1 mg/kg IV morphine and 1 g oral paracetamol every six hours and 200 mg oral celecoxib on the evening of the operation and in the morning and evening of the following day. Patients who needed pain medication after the first day received 600 mg oral ibuprofen every six hours and 1 g paracetamol every six hours. Rescue medication consisted of 15 g oral morphine.

Sample Characteristics:

  • The sample was composed of 200 patients.
  • Mean patient age was 62.7 years (SD = 12.5 years).
  • All patients were female.
  • All patients had breast cancer; 42% underwent a mastectomy and 58% had breast-conserving surgery.

Setting:

  • Single site
  • Inpatient
  • Denmark

Study Design:

Prospective trial

Measurement Instruments/Methods:

Four-point symptom rating scale, 0= no complaints and 3 = severe complaints

Results:

  • In the first 36 hours, at rest after surgery, 30.3% of patients reported moderate to severe pain and 69.7% reported light to no pain.
  • Of all patients, 22% required rescue morphine doses. The average total morphine used was 7.5 mg. The mean amount of morphine used was 2.2 mg (SD = 4.3 mg).
  • Of all patients, 79% had no nausea or vomiting.
  • The most common postoperative complaints were of dizziness, headache, diplopia, confusion, and memory disorder. These were similar to complaints present after administration of the preoperative regimen.

Conclusions:

The preoperative drug combination used here appeared to be effective in preventing postoperative nausea and vomiting and may have reduced postoperative pain at rest.

Limitations:

  • The study had a risk of bias due to no appropriate control group.
  • The method of measuring pain and other symptoms is questionable.
  • Whether grading was based on patient self-report or decided by hospital staff is unclear.
  • The report reveals substantial differences in morphine intake based on subgroups of surgical extent; however, the sample was not large enough for authors to complete relevant subgroup analysis.
  • All patients in this study received the same anesthetic regimen, so findings may not be applicable to individuals who receive different anesthesia.
  • Whether pain rating was done only at rest or at rest and with mobilization is unclear.
  • Only patients undergoing mastectomy were included. Findings may not apply to other surgical groups.

Nursing Implications:

The specified combination of medications, administered preoperatively, appeared to reduce some postoperative symptoms in patients who had breast cancer surgery.

Samulak, D., Michalska, M., Gaca, M., Wilczak, M., Mojs, E., & Chuchracki, M. (2011). Efficiency of postoperative pain management after gynecologic oncological surgeries with the use of morphine + acetaminophen + ketoprofen versus morphine + metamizol + ketoprofen. European Journal of Gynaecological Oncology, 32(2), 168–170.

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Study Purpose:

To compare the efficacy of two medication schemes for the management of pain after gynecologic surgery

Intervention Characteristics/Basic Study Process:

Consecutive patients were randomly assigned to two groups. Group 1 received, on the day of surgery, 1 mg morphine/10 kg body mass subcutaneously (SC) every four hours. After surgery Group 1 received 1 g acetaminophen IV every six hours and 500 mg naproxen per rectum every 12 hours daily. Group 2 received 1 mg morphine/10 kg body mass SC every 4 hours, 1 g metamizol IV every 6 hours, and 500 mg naproxen per rectum every 12 hours. For all patients, in instances of pain rated 5 or more, an additional 100 mg of ketoprofen IV was administered. Pain was rated throughout hospitalization.

Sample Characteristics:

  • The sample was composed of 128 patients.
  • Mean patient age was 68 years; the age range of patients was 42–82 years.
  • All patients were female.
  • All patients underwent operations of category III or IV, a classification indicating extensive tissue injury and significant postoperative acute pain.

Setting:

  • Single site
  • Inpatient
  • Poland

Study Design:

Randomized parallel group

Measurement Instruments/Methods:

Numeric pain rating scale of  0–10

Results:

  • Patients in group 1 had significantly less pain than did the other group (p < 0.05).
  • On the operative day, 34% of group 1 patients required rescue medication compared to 52% of patients in group 2.
  • By postoperative day 3, 3.12% of group 1 patients required rescue medication compared to 4.69% in group 2.
  • During the entire postoperative period, no side effects were associated with either treatment regimen.

Conclusions:

For the management of postoperative pain following gynecologic surgery, the combination of morphine, acetaminophen, ketoprofen, and metamizol as used in this study was more effective than the combination of morphine, metamizol, and ketoprofen.

Limitations:

  • Authors did not report the anesthesia regimen used.
  • Authors did not analyze the demographic differences or other factors, such as type of surgery, that could impact pain scores.

Nursing Implications:

This study describes a perioperative pain management regimen that appears to have decreased the pain of patients who underwent  extensive gynecologic surgery. Note, however, that the more effective regimen did not provide complete control for more than 30% of patients on the day of surgery and for more than 15% on the first postoperative day. This study adds to the growing research regarding  perioperative adjuvant medications for acute pain control.

Systematic Review/Meta-Analysis

Yan, P.Z., Butler, P.M., Kurowski, D., & Perloff, M.D. (2014). Beyond neuropathic pain: Gabapentin use in cancer pain and perioperative pain. The Clinical Journal of Pain, 30, 613–629.

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Purpose:

STUDY PURPOSE: To conduct a clinical evidence review of gabapentin's use in the management of perioperative pain and cancer-related pain
 
TYPE OF STUDY: Systematic review

Search Strategy:

DATABASES USED: PUBMED and Ovid MEDLINE
 
KEYWORDS: Surgery and cancer, both cross-referenced with gabapentin and pain
 
INCLUSION CRITERIA: Clinical trial studies for the treatment of cancer-related and surgical pain with the quality of evidence at level II-2 or higher; nonhuman studies were included for cancer-related pain
 
EXCLUSION CRITERIA: Nonblinded studies, case reports that did not present a unique finding, and studies that focused on neuropathic pain only

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: 142
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Each abstract was read by two reviewers and was excluded or included based on the criteria detailed in the search strategy. The resulting references were then read, reviewed, analyzed, and discussed with special attention to clinical trials with the quality of evidence at a level II-2 or higher (as defined by Berg, A., & Allan, J. (2001). Introducing the third US Preventive Services Task Force. American Journal of Preventive Medicine, 20, 21–35.)

Sample Characteristics:

  • FINAL NUMBER STUDIES INCLUDED = 48 
  • TOTAL PATIENTS INCLUDED IN REVIEW = Unknown
  • SAMPLE RANGE ACROSS STUDIES: 20–498 patients
  • KEY SAMPLE CHARACTERISTICS: Patients with cancer-related pain treated with gabapentin and postsurgical patients with related pain being treated with gabapentin

Phase of Care and Clinical Applications:

APPLICATIONS: Pediatrics, elder care, and palliative care 

Results:

Gabapentin was found to be effective in reducing pain and the use of analgesics when used perioperatively for otolaryngology, orthopedic, abdominal, and pelvic surgeries as well as mastectomies. There was scant efficacy noted following cardiothoracic surgery. Studies of cancer-related pain management regimens that included gabapentin demonstrated a substantial outcome, which included mild to moderate pain relief with increased efficacy noted in patients with neuropathic pain as well as cancer-related pain.

Conclusions:

Gabapentin was proved to be therapeutic as an adjuvant treatment for cancer-related pain. The authors found multiple studies concluding that gabapentin was effective as part of an analgesic regimen for cancer-related pain. They also effectively described the results of double-blinded, randomized, placebo-controlled research supporting the conclusion in favor of the perioperative use of gabapentin as an adjuvant analgesic.

Limitations:

The articles that were reviewed incorporated disproportionately more patients with breast, lung, and colorectal cancers.

Nursing Implications:

Nurses are in a position to gather additional data and contribute to research, providing more evidence to support the use of gabapentin as an adjuvant analgesic as a part of an effective procedure in the case of perioperative pain. Nurses also are in a position to provide efficient research reviews of studies that evaluate the effect of gabapentin.

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