Nicotine Administration and Post-operative Opioid Use With Bariatric Surgery

NCT ID: NCT01194089

Last Updated: 2015-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2014-04-30

Brief Summary

This prospective, randomized, double-blind study will enroll nonsmoking female subjects undergoing laparoscopic bariatric surgery under general anesthesia. The hypothesis of this study is that female nonsmokers who receive nicotine via nasal spray immediately before waking up from anesthesia will need less pain medications 24 hours after the surgery compared to the subjects who receive placebo spray.

Detailed Description

Though nicotine is known to be a mild analgesic, its use in the peri-operative period to reduce postoperative opioid requirements has only recently been investigated. In nonsmokers it has been shown to reduce postoperative pain and opioid requirements in both female patients undergoing uterine surgery and male patients undergoing prostatectomy. We have recently confirmed these findings in women undergoing uterine surgery by open, laparoscopic and vaginal approaches. In this study we found a 30% mean reduction of 24 hour postoperative opioid requirements following the administration of a 3 mg dose of nicotine nasal spray. Two previous studies with perioperative transdermal nicotine found that increasing doses of nicotine and increasing serum levels of nicotine were associated with higher rates of nausea. In our study, we found that the administration of nasal nicotine was associated with a transient increase of postoperative nausea and vomiting (PONV), but this was limited to the recovery room (PACU) stay. Two studies of nasal nicotine where antiemetics were prophylactically administered did not report the incidence of nausea. In our study, antiemetics were used as rescue medications only. Thus, it is unclear if the prophylactic administration of anti-emetics would effectively counteract the transient emetogenic effect of a small dose of nasal nicotine.

Laparoscopic bariatric surgery is becoming an increasingly popular treatment of morbid obesity. We recently performed a detailed analysis of postoperative pain and opioid requirements among patients that had this type of surgery and found that among non-smokers severe pain (pain > 7/10 on a 10 point scale) was commonly experienced (35%) despite substantial amount of postoperative opioid use (mean 68 mg oral morphine equivalents) and non-opioid analgesics in the first 24 hours. Because obesity related sleep disorders exceed 70% of patients undergoing bariatric surgery, and those disorders are exacerbated by opioids, potential therapies that could reduce postoperative opioid requirements in these patients have substantial value. Further, delayed nausea often poses a problem for these patients meeting hospital discharge criteria, and opioids used for analgesia aggravates this problem. Thus, the use of nasal nicotine could reduce the amount of opioid these patients require for postoperative analgesia. Combined with aggressive antiemetic prophylaxis against PONV, nasal nicotine could paradoxically and indirectly reduce the incidence of nausea in these patients by decreasing postoperative opioid requirements. The proposed study is a randomized clinical trial examining how nicotine affects recovery of female non-smokers undergoing bariatric surgery from general anesthesia. We will test the hypothesis that nicotine, administered in a nasal spray immediately before emergence from anesthesia, will reduce postoperative opioid requirement and postoperative pain. A secondary outcome is to assess if the routine administration of prophylactic antiemetic therapy prevents increased PONV associated with nicotine administration.

Conditions

Pain, Postoperative

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nasal Nicotine Spray

3 mg of nasal nicotine will be administered postoperatively.

Group Type: ACTIVE_COMPARATOR

Nasal Nicotine Spray

Intervention Type: DRUG

Single 3 mg dose of nasal nicotine spray

Nasal Normal Saline Spray

1 ml of nasal normal saline spray will be administered postoperatively.

Group Type: PLACEBO_COMPARATOR

Nasal Normal Saline Spray

Intervention Type: DRUG

An isotonic solution of sodium chloride 0.65% in deionized water

Interventions

Nasal Nicotine Spray

Single 3 mg dose of nasal nicotine spray

Intervention Type: DRUG

Nasal Normal Saline Spray

An isotonic solution of sodium chloride 0.65% in deionized water

Intervention Type: DRUG

Other Intervention Names

Nicotrol NS; Rhino-Mist; Salinex; Ocean Nasal Spray

Eligibility Criteria

Inclusion Criteria

• American Society of Anesthesiologists (ASA) class 2-3
• Non-smokers, defined as not smoking (not even a puff) for at least one year preoperatively, and having smoked less than 100 cigarettes throughout their life or remote history of smoking with complete tobacco abstinence (not even a puff) for at least 10 years
• Scheduled for elective laparoscopic bariatric surgery (other than gastric banding or sleeve resection bariatric surgeries as these are outpatient procedures) requiring general anesthesia.

Exclusion Criteria

• Regular use of opioid medications in the past year, any prior use of sustained release opioid medications, or history of substance abuse with opioids
• History of previous psychiatric hospitalizations
• Allergy to nicotine
• Previous bariatric surgery or previous foregut surgery
• Pregnant or lactating female (per usual surgical routine)
• Contraindications for receiving ketorolac (elevated creatinine)
• Unstable angina, severe uncontrolled hypertension, serious cardiac dysrhythmias (tachyarrhythmias, atrial fibrillation), or vasospastic diseases (Buerger's disease, Raynaud's phenomena)
• Unable to provide informed consent to participate in the study
• Contraindication to the proposed antiemetics.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Toby Weingarten

OTHER

Sponsor Role: lead

Responsible Party

Toby Weingarten

Associate Professor of Anesthesiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Toby Weingarten, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

Weingarten TN, McGlinch BP, Liedl L, Kendrick ML, Kellogg TA, Schroeder DR, Sprung J. Intranasal nicotine increases postoperative nausea and is ineffective in reducing pain following laparoscopic bariatric surgery in tobacco-Naive females: a randomized, double blind trial. Obes Surg. 2015 Mar;25(3):506-13. doi: 10.1007/s11695-014-1431-7.

Reference Type: RESULT

PMID: 25190522 (View on PubMed)

Other Identifiers

10-002241

Identifier Type: -

Identifier Source: org_study_id