Multimodal Analgesia in Patients with Morbid Obesity

This ongoing column is authored by members of the International Society for the Perioperative Care of the Obese Patient (ISPCOP), an organization dedicated to the bariatric patient.

Column Editor: Stephanie B. Jones, MD

Dr. Jones is Associate Professor, Harvard Medical School and Vice Chair for Education, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

This month’s installment by Preet Mohinder Singh, MD; and Anupama Wadhwa, MD

Dr. Preet Mohinder Singh is Assistant Professor, Department of Anesthesia, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Dr. Anu Wadhwa is Residency Curriculum Director, Associate Professor, and Site Director, Outcomes Research Consortium, Department of Anesthesiology and Peri-Operative Medicine, University of Louisville, Louisville, Kentucky.

Funding: No funding was provided.

Disclosures: The authors do not have any conflicts of interest relevant to the content of this article.

ABSTRACT
Patients with morbid obesity pose a challenge for perioperative pain management. High ceiling analgesics-opioids have limited role due to safety concerns for patients with or without obstructive sleep apnea. This article reviews multimodal analgesia options for patients with obesity.

Introduction
Patients with morbid obesity pose a challenge for perioperative pain management. High ceiling analgesics-opioids have limited role due to safety concerns for patients with or without obstructive sleep apnea (OSA). More surgeries are being performed laparoscopically over the last couple of decades. This has led to decreased analgesic requirements and promoted expedited recovery. Despite this, postoperative pain still remains the prime factor of patient dissatisfaction toward surgical experience.[1]

Postoperative complications in patients with morbid obesity have been consistently linked to increasing body mass index (BMI), and the use of opioids has been found to have strong association in precipitating the same. Patients with morbid obesity show unique physiological alterations that modify both pharmacokinetics and pharmacodynamics of opioids eventually predisposing them to increased sensitivity towards unwanted sedative effect.
Bearing these concerns in mind it is not uncommon to undertreat perioperative pain in patients with morbid obesity. Instead of relying primarily upon opioids, one must use combinations of analgesics that act by different mechanisms and add to analgesic efficacy rather than adverse effects.
Editor’s note: Most drug recommendations mentioned in this article are based on total body weight (TBW).

Obesity, Opioids, and OSA
Significant research in recent years has focused on the relationship between obesity and OSA. BMI more than 28kg/m2 is associated with a five-fold higher incidence of OSA. Forty-two to 55 percent of men with obesity have a apnea-hypopnea index (AHI) of more than 15, and 16 to 24 percent women have AHI greater than 15 on polysomnography studies. Seventy-seven to 91 percent of patients with morbid obesity have OSA.[2]

The pathophysiology of OSA is intimately linked to obesity. Both anatomical and physiological alterations in pharynx predispose to airway collapse in patients with morbid obesity during even slight loss of pharyngeal muscle tone.[3,4] An inverse relation between obesity and pharyngeal area has been clearly demonstrated on magnetic resonance imaging (MRI)-based studies. Additionally, deposition of adipose tissue into pharyngeal structures, such as the uvula, tonsils, tonsillar pillars, tongue, aryepiglottic folds, and, most importantly, the lateral pharyngeal walls, play a pivotal role in development of OSA. The deposition of extra luminal fat around the airway further increases the collapsibility of the airway. The relationship becomes more important when opioids are used as analgesics perioperatively in these patients.
While OSA is not uncommon in patients on opioids, central sleep apnea was induced in almost 30 percent of nonobese patients receiving methadone maintenance therapy for substance abuse de-addiction.[5] Opioids being central depressants diminish the action of the pharyngeal dilator muscles in adult patients with obesity and OSA. During the initial three days postoperatively, pain scores are highest. This high pain suppresses Stages 3 and 4 (deep sleep phase) of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Opioids promote deep sleep if used during the first three postoperative days (by direct central action), and apnea during drug-induced sleep is increased. Opioids also alter the natural sleep architecture by promoting NREM and REM phase of sleep.[6] Subsequently during the next three days, natural deep REM sleep rebounds. In this phase of recovery, the danger of life-threatening natural deep sleep-induced apnea again increases. Thus as a result of opioid use in obesity with OSA, the likely incidence of airway obstruction not only increases during opioid therapy, but also after cessation of opioids as well.[7] Therefore, it is not surprising that as per the American Society of Anesthesiologists (ASA) closed claims database, patients with obesity account for almost 48 percent of adverse respiratory events secondary to opioids.[8]

Opioids also increase sensitivity (pharmaco-dynamic variation) to therapeutic doses producing unpredictable results. Similarly, increased central sensitivity has also been confirmed in animal studies where comparable opioid doses in obese mice were shown to possess much higher potential for respiratory depression.[9] Therefore, for safety concerns, analgesic techniques in patients with morbid obesity must be tailored to achieve optimal analgesia with minimal or even no opioids (opioid-free analgesia).

Multimodal analgesia approach in morbid obesity    
The benefits of targeting different analgesic mechanisms can be used to achieve unique advantages in patients with obesity. By using these principles in bariatric patients, doses of individual agents (more importantly opioids) can be reduced, and thus, precipitation of OSA perioperatively can be avoided.10 The various pharmacological approaches that can be clinically used include the following:
•    Modulation pain afferents to the brain
•    Alleviating central perception of pain
•    Enhancing pain inhibitory pathways.

The modulation of central perception of pain as brought about by opioids is therapeutically limited in patients with morbid obesity, thus the other targets must take priority in these patients. The drugs utilizing the above principles are shown in Figure 1. In patients with morbid obesity, regional anesthesia and analgesia must be preferred despite the procedural/technical challenges. This not only gives the opportunity to cut down on opioids, but also avoids the use of anesthetic agents that may have residual action (e.g., inhalation agents) of clinical significance in obese.

Analgesia and perioperative complications in morbid obesity
Fear of side effects, such as respiratory depression, over sedation, nausea, and vomiting, from opioid use in patients with morbid obesity often leads to under treatment of pain. Inadequate analgesia indirectly contributes to multiple postoperative complications in patients with morbid obesity. In abdominal surgeries, pain prevents deep breathing and further adds to basal lung atelactasis in this patient population. Joris et al[11] demonstrated that postoperative analgesia is directly related to improvement in postoperative pulmonary function tests in patients with morbid obesity undergoing abdominal surgery. Superior pain relief can prevent development of hypoxemia, atelectasis, and pneumonia.12 Similarly, adequate analgesia promotes early ambulation. This becomes all the more important in this patient population where deep vein thrombosis rates are significantly higher than normal population.[13–15]

Non-opioid systemic analgesics
Agents that have a mechanism of action at site distant from actual painful area exert analgesic effect by various mechanisms. In patients with morbid obesity, pain is best treated with intravenous (IV) rather than intramuscular (IM) medication. Unless extra-long needles are used, medications intended for the muscle are often delivered instead into the more superficial adipose tissue. Drug absorption is inconsistent from fatty tissue thus possibly leading to inadequate pain control. Also, unlike opioids, increasing doses beyond particular dose range does not add to additional analgesia.[16]
Systemic analgesics can be divided into 1) primary analgesics and 2) adjuvants.

Nonsteroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) offer pain relief by inhibition of cyclo-oxygenase (COX). Their efficacy is well established for mild to moderate pain during the postoperative period. Govindrajan et al[17] demonstrated favorability of perioperative ketorolac in comparision to remifentanil for analgesia, early discharge, and better intraoperative hemodynamic stability in patients with morbid obesity undergoing abdominal laparoscopic surgeries. For short-term postoperative use in bariatric surgery, NSAIDs have shown to be fairly safe with minimal platelet dysfunction or renal/gastrointestinal adverse effects.18 During the initial postoperative period, we suggest using scheduled NSAIDs around the clock instead of as needed (i.e., time-based rather than analgesic demand based)

Paracetamol. Unlike NSAIDs, paracetamol has central mechanism of action related to its ability to suppress COX-3 in the hypothalamus.[19] It is devoid of renal, hematological, and gastrointestinal adverse effects that limit the use of NSAIDs. In morbid obesity, use of paracetamol with low doses of narcotics allows patients to be managed in high dependency units rather than critical care units due to its opioid sparing effect.[20]

Bergland et al[21] also demonstrated the efficacy of paracetamol in safe management of patients undergoing laparoscopic gastric bypass using it as a component of multimodal opioid-free analgesia. Most patients with morbid obesity during the immediate postoperative period may need additional analgesic supplementation in addition to around-the-clock IV paracetamol for optimal analgesia.

Systemic adjuvants
To avoid opioids, many additional drugs that enhance the analgesia directly or indirectly in postoperative period have been tried. These drugs must be used in conjunction with frontline analgesics.

Ketamine. Ketamine is a phencyclidine derivative with N-Methyl-D-aspartate (NMDA) antagonistic properties. When used in small doses of 0.2mg/kg, it is an analgesic, anti-hyperalgesic and prevents opioid induced tolerance. A key advantage of ketamine in patients with morbid obesity is that it synergizes opioid adds onto analgesia without suppression of respiratory drive or loss of airway tone.[9] Sollazzi et al[22] demonstrated that pre-induction ketamine infusion in patients with morbid obesity undergoing bilio-pancreatic diversion for weight loss surgery was associated with early extubation and diminished postoperative analgesic requirements. In multiple analyses, ketamine has shown to have effective lower analgesic requirements and cut down on total opioids significantly for first 48 hours after the surgery.[23,24] Evidence suggests that a postoperative infusion dose of up to 2.5mcg/kg/min is well tolerated with minimal cognitive impairment and hallucinations.[25]

Dexmedetomidine. Dexmedetomidine is an alpha-2 blocker that has selectivity for alpha-2a receptors that have roles in analgesia and sedation.[26] Unlike its predecessor clonidine, it has significantly more selectivity for analgesic/sedative actions with much lesser hemodynamic adverse effects. Intraoperative dexmedetomidine infusion reduces both intraoperative and postoperative opioid requirements in addition to providing more stable hemodynamics in patients with morbid obesity, when compared to patients without any supplemental dexmedetomidine infusion.[27]

Ramsay et al[28] used dexmedetomidine-based anesthesia in a woman with morbid obesity and severe tracheal stenosis. This highlighted the ability of dexmedetomidine to provide anesthesia without causing apnea or losing airway tone, especially in a highly susceptible patient population, such as those with morbid obesity with OSA. When used in doses lower than 0.4mcg/kg/min, it causes minimal hemodynamic or respiratory compromise.[29]

Pregabalin. The number of studies evaluating the role of pregabalin in the population with obesity is presently limited. However, trials so far have demonstrated that pregabalin used as single-dose premedication in the preoperative phase during bariatric surgery significantly lowers the postoperative analgesic requirement that extends into first postoperative day.[30]

Other additional agents that have been tried in patients with morbid obesity preoperatively to supplement analgesia are magnesium, IV local anesthetic (lidocaine) infusions, and clonidine.[31–33] These agents need more evidence to be adopted in routine perioperative clinical practice.

Regional anesthesia in morbid obesity
Successful regional anesthesia in morbid obesity as a component of multimodal analgesia has potential advantages of avoiding risks of OSA, difficult airway, and pulmonary complications associated with general anesthesia.[3] Patients with obesity not only undergo bariatric surgeries (where regional techniques only supplement general anesthesia), but other surgeries as well. Studies show that this patient population is at least 2.5 times more likely to undergo hip replacements and about 10 times more likely to undergo knee replacements when compared to patients without obesity.[34] Regional anesthesia increases perioperative safety in this patient population for the peripheral surgeries despite the technical challenges associated with regional anesthesia. Regional anesthetic techniques have been clearly linked to better pain relief and early discharge in patients with morbid obesity.35 These techniques can be either used to provide surgical anesthesia or aid in postoperative opioid-free analgesia. The techniques can be divided into central neuraxial blocks and peripheral nerve blocks.

Central neuraxial blocks. Increasing subcutaneous fat obscures the landmarks making identification of spinous processes difficult for central neuraxial block. Thus, positioning these patients (sitting with best possible flexion at spine) is very critical for the success of the block performance.36 Since the spaces are deep, it must be realized that slight deviation at skin entry point can make large deviations of needle tip off the targeted area. It is preferable that a very experienced anesthesiologist be involved whenever regional techniques are planned in patients with morbid obesity.
Sub-arachnoid block/spinal anesthesia is primarily limited to surgical anesthesia (using local anesthetics) and, as per ASA practice guidelines, wherever possible intrathecal water-soluble opioids should be avoided in patients with morbid obesity.[37] Intrathecal adjuvants like clonidine, dexmedetomidine, magnesium, and dexamethasone have been used to prolong the analgesia after effects of local anesthetics wear off.[38–40] Continuous epidural techniques using local anesthetics via a catheter have shown favorable results in terms of respiratory function and return of bowel function.[41–43]

In patients with obesity undergoing off-pump coronary artery bypass surgery, thoracic epidural catheter with postoperative infusion of local anesthetics was found to be associated with better analgesia, early tracheal extubation, and shorter intensive care unit (ICU) stay.[44] Von Ungern-Sternberg et al[45] compared the conventional opioid-based analgesia with thoracic epidural analgesia technique in patients with obesity undergoing upper abdominal and open gynecological procedures and reported that patients could be discharged earlier as a result of significantly quicker recovery of spirometric values in patients receiving epidural analgesia.[45]

Peripheral nerve blocks. Nielsen et al[46] conducted an extensive review evaluating success of peripheral nerve blocks. They demonstrated that obesity was associated with higher block failure and complication rates in surgical regional anesthesia in the ambulatory setting.[46] However, multiple trials have reported that various upper limb blocks in patients with morbid obesity have only marginally lower success rate when compared to nonobese patients, and thus patients with morbid obesity should not be excluded from regional anesthesia.[47,48] Often, patients with obesity have more fat in their lower limbs, thus lower limb blocks may be technically more challenging with landmark techniques, and one may have to resort to neuraxial blockade in such cases.

Ultrasound and regional anesthesia in morbid obesity
A high BMI obscures the landmarks that ultrasound may help to delineate. Successful use of ultrasound for improving success rates of central neuraxial blocks in patients with morbid obesity has been reported.[49] Use of imaging has also shown to improve neuraxial block success in the hands of relatively less experienced residents.[50] Preferably newer ultrasound machines should be capable of visualizing deeper tissue than that used conventionally (i.e., lower frequency probe may be needed). Portable ultrasound has shown to improve accuracy of interscalene block similar to that seen in nonobese patients.51 Lower limb blocks still remain challenging due to requirement of deeper penetration by the ultrasound,[52] although isolated reports of success do exist in patients with morbid obesity.[53] Saranteas[54] demonstrated that ultrasound wave attenuates in quality while visualizing deeper structures, and thus, image quality is affected. This can be dealt with by using 3D ultrasound reconstruction technology if available.[55]

Future directions for analgesia
Opioid sparing multimodal analgesia can be further strengthened by use of innovative strategies. Pre-emptive analgesia by obtunding nociceptive responses prior to surgical stimulus can reduce postoperative pain and also lowers the incidence of conversion of acute pain to chronic pain.[56] In patients with morbid obesity, NSAIDs are a safe and effective option for pre-emptive analgesia.[57] Postoperative patient-controlled IV analgesia or epidural analgesia is known to lower opioid consumption with a high degree of patient satisfaction and adequate analgesia.[58] Once a patient’s understanding for equipment is assured, we recommend using patient-controlled analgesia modalities preferentially. Additional techniques, such as long-acting local anesthetic infusion at surgical wound site or even intraperitoneal infusion have shown promising pain relief.[59,60] Limitations of opioid use often lead to under treatment of pain in patients with morbid obesity, thus increasing postoperative morbidity.[61] The use of multimodal approach for analgesia can serve as a remedy for both opioid underdosing or overdosing, thus improving patient satisfaction toward surgery in patients with morbid obesity.

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Category: Anesthetic Aspects of Bariatric Surgery, Past Articles