Nicotine Administration and Post-operative Opioid Use With Bariatric Surgery

• ClinicalTrials.gov Identifier: NCT01194089
• Recruitment Status: Completed
• First Posted: September 2, 2010
• Results First Posted: June 3, 2015
• Last Update Posted: July 9, 2015
• Sponsor: Toby Weingarten
• Information provided by (Responsible Party): Toby Weingarten, Mayo Clinic

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative	Drug: Nasal Nicotine Spray; Drug: Nasal Normal Saline Spray	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Study to Evaluate the Efficacy of Nasal Nicotine Spray to Reduce Post-Operative Opioid Requirements in Nonsmokers in Elective Laparoscopic Bariatric Surgical Patients
• Study Start Date: August 2010
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Nasal Nicotine Spray; 3 mg of nasal nicotine will be administered postoperatively.	Drug: Nasal Nicotine Spray; Single 3 mg dose of nasal nicotine spray; Other Name: Nicotrol NS
Placebo Comparator: Nasal Normal Saline Spray; 1 ml of nasal normal saline spray will be administered postoperatively.	Drug: Nasal Normal Saline Spray; An isotonic solution of sodium chloride 0.65% in deionized water; Other Names: Rhino-Mist; Salinex; Ocean Nasal Spray

Outcome Measures

Primary Outcome Measures :

1. Postoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours Postoperatively [ Time Frame: During PACU stay (approximately 94 minutes after operation), 24 hours after operation ]
   Opioid use was calculated in intravenous morphine equivalents (iv MEQ) according to the Mayo Clinic Pharmacy opioid conversion calculator based on the recommendations from the American Pain Society. Specifically, the following conversion was used: 10 mg in MEQ=100mcg iv fentanyl=1.5 mg iv hydromorphone=20mg oral oxycodone=30mg oral hydrocodone.

Secondary Outcome Measures :

1. Number of Participants Who Needed to Use Antiemetic Medication in the PACU [ Time Frame: 24 hours postoperatively. ]
   Rescue antiemetic therapy was 0.625 mg droperidol. Recalcitrant postoperative pain, nausea and vomiting (PONV) was treated per discretion of the supervising anesthesiologist.
2. Numeric Pain Score [ Time Frame: on admission, 30 minutes, 60 minutes, at discharge ]
   Upon arrival in the PACU and at least every 30 minutes thereafter while in the PACU, the subject was asked to report pain using a numerical pain score for current pain at rest from 0 (representing no pain) to 10 (representing the worst imaginable pain).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Toby Weingarten

Investigators

• Principal Investigator: Toby Weingarten, MD; Mayo Clinic

More Information

Publications of Results:

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-Naïve females: a randomized, double blind trial. Obes Surg. 2015 Mar;25(3):506-13. doi: 10.1007/s11695-014-1431-7. Erratum in: Obes Surg. 2015 Sep;25(9):1764-5.

• Responsible Party: Toby Weingarten, Associate Professor of Anesthesiology, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01194089
• Other Study ID Numbers: 10-002241
• First Posted: September 2, 2010
• Results First Posted: June 3, 2015
• Last Update Posted: July 9, 2015
• Last Verified: June 2015

Keywords provided by Toby Weingarten, Mayo Clinic:

Nicotine; Postoperative pain; Bariatric surgery

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action