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Nicotine Administration and Post-operative Opioid Use With Bariatric Surgery

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

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01194089
Enrollment
95
Registered
2010-09-02
Start date
2010-08-31
Completion date
2014-04-30
Last updated
2015-07-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain, Postoperative

Keywords

Nicotine, Postoperative pain, Bariatric surgery

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.

Interventions

DRUGNasal Nicotine Spray

Single 3 mg dose of nasal nicotine spray

DRUGNasal Normal Saline Spray

An isotonic solution of sodium chloride 0.65% in deionized water

Sponsors

Toby Weingarten
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 60 Years
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Postoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours PostoperativelyDuring PACU stay (approximately 94 minutes after operation), 24 hours after operationOpioid 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

MeasureTime frameDescription
Number of Participants Who Needed to Use Antiemetic Medication in the PACU24 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.
Numeric Pain Scoreon admission, 30 minutes, 60 minutes, at dischargeUpon 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).

Countries

United States

Participant flow

Recruitment details

Subjects were enrolled at Mayo Clinic in Rochester, Minnesota from August 2010 to March 2014.

Pre-assignment details

95 subjects randomized; 48 to Placebo arm, and 47 to Nicotine arm. On the Placebo arm one subject had their surgery rescheduled and did not take part in the study, leaving 47 starting. On the Nicotine arm 3 subjects withdrew consent prior to surgery and 1 subject's surgery was cancelled, and 1 subject surgery rescheduled, leaving 42 starting.

Participants by arm

ArmCount
Nasal Nicotine Spray
3 mg of nasal nicotine will be administered postoperatively.
42
Nasal Normal Saline Spray
1 ml of nasal normal saline spray will be administered postoperatively.
47
Total89

Baseline characteristics

CharacteristicNasal Nicotine SprayNasal Normal Saline SprayTotal
Age, Continuous46.0 years
STANDARD_DEVIATION 9.1
44.9 years
STANDARD_DEVIATION 10.6
45.8 years
STANDARD_DEVIATION 9.9
Region of Enrollment
United States
42 participants47 participants89 participants
Sex: Female, Male
Female
42 Participants47 Participants89 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
28 / 4224 / 47
serious
Total, serious adverse events
2 / 421 / 47

Outcome results

Primary

Postoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours Postoperatively

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.

Time frame: During PACU stay (approximately 94 minutes after operation), 24 hours after operation

ArmMeasureGroupValue (MEDIAN)
Nasal Nicotine SprayPostoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours PostoperativelyDuring the PACU stay5.3 mg
Nasal Nicotine SprayPostoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours PostoperativelyFirst 24 hours postoperatively39.6 mg
Nasal Normal Saline SprayPostoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours PostoperativelyDuring the PACU stay5.2 mg
Nasal Normal Saline SprayPostoperative Opioid Use During the Postanesthesia Care Unit (PACU) Stay, and the First 24 Hours PostoperativelyFirst 24 hours postoperatively32.7 mg
Comparison: Comparison between arms for the postoperative opioid use during the postanesthesia care unit (PACU) stay, using a one tailed P value.p-value: 0.828Wilcoxon (Mann-Whitney)
Comparison: Comparison between the arms for the first 24 hours postoperatively, using a one tailed P value.p-value: 0.752Wilcoxon (Mann-Whitney)
Secondary

Number of Participants Who Needed to Use Antiemetic Medication in the PACU

Rescue antiemetic therapy was 0.625 mg droperidol. Recalcitrant postoperative pain, nausea and vomiting (PONV) was treated per discretion of the supervising anesthesiologist.

Time frame: 24 hours postoperatively.

ArmMeasureValue (NUMBER)
Nasal Nicotine SprayNumber of Participants Who Needed to Use Antiemetic Medication in the PACU24 participants
Nasal Normal Saline SprayNumber of Participants Who Needed to Use Antiemetic Medication in the PACU12 participants
Comparison: Comparison between the arms for antiemetic medication use in the PACU.p-value: 0.002Chi-squared
Secondary

Numeric Pain Score

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).

Time frame: on admission, 30 minutes, 60 minutes, at discharge

Population: Not all participants completed the pain scale at every time point. The participants analyzed per arm (nicotine, normal) at each time point were: on admission (40, 45); 30 minutes (40, 47); 60 minutes (34, 40); at discharge (39, 44),

ArmMeasureGroupValue (MEDIAN)
Nasal Nicotine SprayNumeric Pain ScoreAt discharge3 units on a scale
Nasal Nicotine SprayNumeric Pain Score60 minutes4 units on a scale
Nasal Nicotine SprayNumeric Pain ScoreOn admission0 units on a scale
Nasal Nicotine SprayNumeric Pain Score30 minutes5 units on a scale
Nasal Normal Saline SprayNumeric Pain Score60 minutes4 units on a scale
Nasal Normal Saline SprayNumeric Pain Score30 minutes5 units on a scale
Nasal Normal Saline SprayNumeric Pain ScoreOn admission3 units on a scale
Nasal Normal Saline SprayNumeric Pain ScoreAt discharge3 units on a scale
Comparison: The arms were compared for numeric pain score on admission.p-value: 0.354Wilcoxon (Mann-Whitney)
Comparison: The arms were compared for numeric pain score at 30 minutes.p-value: 0.492Wilcoxon (Mann-Whitney)
Comparison: The arms were compared for numeric pain score at 60 minutes.p-value: 0.809Wilcoxon (Mann-Whitney)
Comparison: The arms were compared for numeric pain score at discharge.p-value: 0.381Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026