Dexmedetomidine in Bariatric Surgery: A Useful Opioid Adjunct? An Evidence-Based Review

Abstract

Background:

According to the Centers for Disease Control, nearly 34% of adults in the United States are obese, and one treatment used is bariatric surgery. However, often these patients require large doses of opioids during the perioperative period, which can result in significant side effects. One agent that can be used as a supplement or in place of opioids is the alpha 2 agonist dexmedetomidine. However, research regarding the use of dexmedetomidine in bariatric surgery is limited. Therefore, the purpose of this evidenced-based review was to examine the effect of dexmedetomidine on anesthetic requirements during bariatric surgery and opioid requirements and recovery in the postoperative period.

Methods:

An evidenced-based review was completed using MEDLINE with a search of articles published after 2005. The terms obesity and bariatric surgery were linked with dexmedetomidine and scored for research quality.

Results:

A total of 182 subjects from three randomized controlled trials, one case review, and two case reports were identified as relevant and included in this analysis. It was noted that when dexmedetomidine was used as part of the anesthesia regimen, there was an overall decrease in intraoperative opioid analgesics and inhalational anesthetics, as well as an increased stability in intraoperative hemodynamics. Postoperatively, those patients receiving dexmedetomidine were noted to require less postoperative analgesia and had decreased pain scores with no reported incidences of respiratory depression.

Conclusions:

Based on this review, it appears that dexmedetomidine is a useful intraoperative anesthetic adjunct in patients undergoing bariatric surgery.

Introduction

Two-thirds of the United States population is classified as overweight or obese. This is a recent trend; for example, in 1990 10 states reported an obesity ratio of less than 10%, but in 2010 all states reported an obesity ratio of at least 20%, with 36 states reporting a ratio of greater than 25%.^1,2 This increased incidence of obesity is undoubtedly due to the rising caloric intake in the population, coupled with the lack of effective treatment regimens (diet, exercise, and behavior modification) for obesity.³ Obesity is determined by using weight and height to calculate a number called the body mass index (BMI). A calculated BMI between 25 and 29.9 kg/m² is considered overweight, a BMI greater than 30 kg/m² is considered obese, and a BMI greater than 40 kg/m² is classified as morbidly obese.¹ There are multiple diets and medication regimens that have been used to combat obesity. However, they have been shown only to be marginally effective.⁴ One option shown to be successful in promoting weight loss in the obese individual is bariatric surgery. Bariatric surgery is surgery performed on the stomach and/or intestines to help a person lose weight. The following criteria are used by many surgeons to determine patient eligibility for bariatric surgery:^1–4

1. Unsuccessful in losing weight despite efforts with diet and exercise.

2. BMI >40 kg/m²

3. BMI 35–39.9 kg/m² in patients with serious weight-related comorbidities such as type 2 diabetes, hypertension, or obstructive sleep apnea.

Bariatric surgery is a surgical procedure that involves the upper abdomen. It has been noted that the morbidity and mortality of obese patients is higher than nonobese patients. The weight of the additional adipose tissue can induce pulmonary complications caused by decreased lung compliance, total lung capacity, functional residual capacity, and ineffective gas exchange in the lungs.⁵ These patients are prone to hypoxemia and hypercarbia, and routinely have an increased cardiac workload, which increases their risk for hypertension, coronary artery disease, and cardiac failure.⁵ This poses an increased challenge to anesthesia providers because obese patients are sensitive to the respiratory depressant effects of many of the medications routinely administered in anesthesia, particularly opioids. This places obese patients at risk for inadequate postoperative ventilation.⁵ In particular, obese patients have impaired respiratory mechanics during anesthesia that contribute to postoperative hypoxia and hypercapnea.⁵ This is especially true for a patient undergoing bariatric surgery because these patients are often classified as morbidly obese (BMI >35 kg/m²).

Bariatric surgery has traditionally been performed under general anesthesia using volatile agents and intravenous opioids. The administration of opioids can result in a delayed awakening, as well as respiratory depression well into the postoperative period. The average amount of opioids administered in patients who are undergoing bariatric surgery is between 266 and 396 μg fentanyl administered during the operative procedure and can be as high as 76 mg of morphine administered during postoperative day one, often resulting in some degree of postoperative hyoxemia or hypoventilation.^6,7 Therefore anesthesia practitioners are continually seeking alternative analgesic adjuncts that do not have as significant of an impact on respiration. One agent that has been noted to possibly fit this requirement is the alpha 2 agonist dexmedetomidine.⁵ Dexmedetomidine possesses hypnotic, sedative, anxiolytic, sympatholytic, and analgesic properties, and has been noted to have little impact on hemodynamics and ventilation, thereby making it an ideal analgesic adjunct for many surgical procedures.⁸ However, research regarding the use of dexmedetomidine in obese patients undergoing bariatric surgery is limited. Therefore, the primary purpose of this evidenced-based review was to examine the effect of dexmedetomidine on postoperative ventilation and hypoxemia. The effect on postoperative analgesic requirements, hemodynamics, and intraoperative anesthetic requirements was also considered.

Methods

The following patient-interrention-comparison-outcome (PICO) question was used to search the literature: Can we effectively decrease the risk of postoperative hypoventilation and hypoxemia by decreasing postoperative opioid requirements (O/C) in obese patients undergoing bariatric surgery (P) by using dexmedetomidine intraoperatively (I)?

An evidenced-based review was completed using MEDLINE with a search of articles published after 2005 in order to obtain the most current research on the topic. The terms obesity and bariatric surgery were linked with dexmedetomidine. A synonym used for “bariatric” was “obesity,” and a synonym used for “opioid analgesic” was “narcotic.” These synonyms were used as alternative search strategies during the search for evidence. Only those trials or case reports that described the hemodynamic and postoperative opioid analgesic requirements and effects on respiration were included. The focus of the search was bariatric or morbidly obese patients. Patients with clinically significant brain, cardiac, respiratory, or liver disease were excluded (Table 1).

Table 1.

Literature Search

Date searched	Database	Years searched	Search terms	String of terms	# Hits
October 12, 2010	MEDLINE	2005–2011	Dexmedetomidine obesity	Combined	8
October 15, 2010	MEDLINE	2005–2011	Dexmedetomidine obesity opioid	Combined	4
October 21, 2010	MEDLINE	2005–2011	Dexmedetomidine Bariatric surgery	Combined	10
October 23, 2010	MEDLINE	2005–2011	Dexmedetomidine obesity narcotic	Combined	5

Results

The search yielded five randomized control trials, a letter, two reviews, and two case reports. Each result was scored for research quality based on the Agency for Healthcare Research and Quality's Evidence Hierarchies (Level I–V) and the United Sates Preventive Services Task Force (USPSTF) Grading Scale (Grade A–I). Only those studies or case reports that incorporated the use of dexmedetomidine in the perioperative period were considered for inclusion. A comprehensive review of the literature regarding the adverse effects of dexmedetomidine was also included to provide a basis to compare adverse effects, but it did not add to the overall comparison between the subjects as it related to the incidence of intraoperative and postoperative outcomes measured. A letter to the editor was excluded for lack of research quality and one review and two randomized control trials (RCTs) were excluded for lack of application to this particular research topic.

A total of three RCTs and two case reports with a total of 182 subjects were identified as relevant and included in this analysis (Table 2). The three RCTs were graded as containing level II B strength evidence, and all examined the effects of intraoperative dexmedetomidine versus placebo (normal saline) or fentanyl on intraoperative and postoperative outcomes in morbidly obese patients undergoing bariatric surgery. All three RCTs were either single or double blinded and used similar measurements to determine overall analgesic requirements, postoperative pain assessment tools, and monitoring of intraoperative and postoperative vital signs and ventilation. All three showed a statistically significant decrease in intraoperative and postoperative analgesic requirements with less of an impact on vital signs and postoperative ventilation as compared to the placebo group.^5,8,9 In addition, all three of the RCTs analyzed other variables that included intraoperative volatile agent requirements, opioid requirements, time to extubation, postoperative nausea, and length of post-anesthesia care unit (PACU) stay.^5,8,9 A more detailed description of each of these RCTs is provided below.

Table 2.

Studies of Dexmedetomidine Use for Bariatric Procedures

Source	Purpose/problem	Sample	Variables	Design	Instruments	Results
Bakhamees et al.⁵	To examine to effect of Dex on anesthetic requirements during surgery, hemodynamic, recovery profile, and morphine use postop	80 morbidly obese pts ASA II or III, age 26–55, scheduled for elective laparoscopic Roux-en-Y gastric bypass	HR & MAP intra & postop Intraop fentanyl & propafol Recovery profile Pain score PCA morphine	Randomized single-blind, placebo controlled	BIS ECG NIBP Pain scale	Decreased use of intraop fentanyl & propofol, decreased intra & postop MAP & HR, decreased pain scores & PCA morphine use postop, better recovery profile, no difference in PONV
Tufanogullari et al.⁸	To evaluate the effect of Dex on early and late recovery after laparoscopic bariatric surgery	80 morbidly obese pts ASA II or III, age 22–66, scheduled for scheduled for laparoscopic gastric banding or bypass	CSI EtDes% MAP & HR Pain scores PACU fentanyl & antiemetics PCA morphine PACU LOS Quality of recovery	Prospective, randomized, double-blind, placebo-controlled dose-ranging	11pt verbal rating scale ECG NIBP Cerebral state index monitor (CSI)	Decreased desflurane requirements, decreased BP, increased phenylephrine requirements, significantly reduced length of PACU stay & PACU fentanyl & antiemetic requirements, no difference in PCA requirements
Feld et al.⁹	To evaluate whether Dex infusion can replace fentanyl for facilitation of gastric bypass surgery	20 pts BMI 54–61, ASA II or III, age 26–55, undergoing open Roux-en-Y gastric bypass	MAP & HR EtDes% Pain scores PCA morphine	Randomized single-blinded, open label	ECG NIBP BIS	Decreased desflurane requirements, decreased BP & HR, decreased time to extubation, decreased PACU pain scores & morphine use, Dex infusion can replace fentanyl
Hofer et al.¹⁰	To describe the anesthetic management of an obese pt undergoing bariatric surgery whose intraop narcotic management was entirely substituted with dex	One	Morbid obesity, Roux-en-Y gastric bypass, postop respiratory depression, narcotics, dex, analgesic	Case report	Careful monitoring of anesthetic course and measurement of postop morphine requirements via PCA	Dex may be a useful anesthetic adjunct for pts who are susceptible to narcotic-induced respiratory depression. In this morbidly obese patient, the narcotic-sparing effects of dex were evident both intraop and postop
Ramsay et al.¹¹	To present a case of respiratory distress in a morbidly obese woman, with severe tracheal stenosis of the third to sixth cartilage and describe the anesthetic management	One	Airway, compromise, α2 adrenergic agonist, dexmedetomidine, morbid obesity, sleep apnea, respiration, depression, surgery, trachea resection	Case report	Careful monitoring of anesthetic course, VS, comfort level, breathing difficulty	High dose dexmedetomidine provided excellent analgesia without respiratory depression. Opioid analgesics were avoided

HR, heart rate; MAP, mean arterial pressure; PCA, patient controlled analgesia; EtDes%, end tidal desflurane percent; PACU LOS, post-anesthesia care unit length of stay; PONV, postoperative nausea and vomiting; CSI, cerebral state index.

Bakhamees et al.⁵ reported the results of a single-blind randomized study that included patients undergoing Roux-en-Y gastric bypass surgery in which 80 patients were randomized to receive either a bolus infusion of 0.8 μg/kg of dexmedetomidine administered on induction of anesthesia followed by an infusion of 0.4 μg/kg of dexmedetomidine, or a placebo. Variables measured included total anesthesia and analgesia requirements during the intraoperative and postoperative periods and vital signs. Intraoperatively assessments were performed by anesthesia providers not blinded to randomized group assignments, whereas all postoperative measurements were performed by PACU nurses blinded to group selection, and all patients were measured in relation to recovery profiles, vital signs, postoperative pain scores, and opioid analgesic requirements via a patient-controlled analgesia (PCA) device were evaluated. Those patients receiving dexmedetomidine were noted to have decreased total analgesic and anesthesia requirements, better control of intraoperative and postoperative hemodynamics, and better overall recovery profiles, which included assessment for adequate ventilation and time to safe extubation as compared to placebo. There were no dropouts in the study. The authors concluded that the use of dexmedetomidine was superior to placebo and resulted superior intraoperative and postoperative outcomes than when traditional opioid-based anesthesia is used.

The double-blinded, placebo-controlled study by Tufanogull et al.⁸ between groups of patients undergoing laparoscopic bariatric surgery that received either a placebo (normal saline) or an infusion of dexmedetomidine of either 0.2 μg/kg/h, 0.4 μg/kg/h, or 0.8 μg/kg/h. A total of 80 patients (20 patients/group) were enrolled in this study. No bolus dose of dexmedetomidine was done prior to initiation of the infusion. The same variables described above in the study by Bakhamees et al. were also measured in this study. There was a noted decrease in overall intraoperative anesthesia requirements in the dexmedetomidine groups as compared to the placebo groups with subsequent decreases in postoperative analgesic and antiemetic requirements. Vital sign measurements and recovery profiles were noted to be similar between the groups. However, those in the dexmedetomidine groups were noted to have a lower overall hemodynamic response to surgery and were discharged from the recovery room earlier that those in the placebo group. Interestingly there were no differences between the 0.2 μg/kg and the 0.8 μg/kg infusion groups, and the authors recommended using a dexmedetomidine infusion of 0.2 μg/kg/h for patients presenting for bariatric surgery.

In the single-blind comparative open label study by Feld et al.,⁹ a total of 20 bariatric surgery patients were randomized to receive either fentanyl 0.5 μg/kg bolus followed by a 0.5 μg/kg/h infusion or dexmedetomidine 0.5 μg/kg bolus followed by 0.5 μg/kg/h infusion. The same variables described in the studies by Tufanogull et al. and Bakhamees et al. were also measured in this study. In addition, Feld et al. measured intraoperative bispectral index (BIS) during the operative procedure. It was noted that those subjects in the dexmedetomidine group had lower volatile agent requirements, more stable vital signs, and were able to achieve a more stable BIS measurement. Postoperatively those in the dexemedetomidine group were also noted to have lower pain scores, better recovery profiles, and required less analagesia. The authors concluded that using dexmedetomidine provided a more stable intraoperative environment and should be considered as a substitute for fentanyl in patients undergoing bariatric surgery.

The two case reports described similar outcomes as those reported in the RCTs, and the authors also recommended using dexmedetomidine as a first line choice for intraoperative analgesia in patients undergoing bariatric surgery.

Discussion

A limitation to all three randomized control trials was the exclusion of all patients with clinically significant brain, cardiac, respiratory (chronic obstructive pulmonary disease [COPD], emphysema, obstructive sleep apnea [OSA]), or liver disease.^5,8,9 Further research is necessary to determine if the use of dexmeditomidine is appropriate to use in this patient population.

The studies by Hofer et al.¹⁰ and Ramsay et al.¹¹ showed that dexmedetomidine provided excellent analgesia without respiratory depression. A limitation of these studies is that they are individual case studies and the conclusions made may not apply to a larger population. A limitation of the Ramsay et al. study is that it is not specific to bariatric surgery. This may mean that the generalized inferences described in this particular study may not apply to other clinical situations.

The study by Haselman et al.¹² provides a comprehensive review of the pharmacology, pharmacokinetics, and adverse effects of dexmedetomidine. It builds a foundation for the use of dexmedetomidine and concludes with suggestions of appropriate patient populations for the use of dexmedetomidine, but does not in itself provide the clinical evidence.

Conclusions

It was shown that when dexmedetomidine was used as part of the anesthesia regimen, there was an overall decrease in the use of opioid analgesics intraoperatively and an increased stability in intraoperative hemodynamics. Some of the limitations noted in the studies included the wide multiple delivery methods and doses used, as well as a failure by the authors to include nonopioid analgesics such as ketorolac or acetamenophin when discussing total analgesic requirements. However, it was noted that inclusion of dexmedetomidine was beneficial in reducing ventilatory effects in all the studies discussed and should be considered as a useful intraoperative anesthetic adjunct in patients undergoing bariatric surgery. However, further research is required.

Footnotes

Disclosure Statement

No competing financial interests exist.

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