The prevalence of obesity continues to rise in the United States and impacts on morbidity, mortality and overall costs in health care considerably. In 2013–2014, more than one-third (37.9%) of U.S. adults were classified as obese, and the prevalence of those with a body mass index (BMI) ≥40kg/m², was 7.7%. (1) The heaviest groups (BMI ≥50kg/m²) increases in prevalence at the fastest rates. (2) Pertinent to healthcare providers—the larger the patient, the more health care resources utilized and the worse the survival. (3) Having a BMI >40kg/m² predicts use of more than double the healthcare dollars of a normal weight individual. (4)

Providing care to individuals with severe obesity is complex, as the physiologic changes associated with morbid and super obesity alter the pharmacokinetic properties of most drugs. (5) Derangements in cardiovascular and respiratory physiology make the patients with morbid obesity more vulnerable to drug-induced respiratory depression and upper airway obstruction, thus increasing the risk of treating them with opioids. In reviewing the literature, it appears that much of what is understood regarding the care of patients with super obesity must be extrapolated from what is known regarding the morbidly obese, a group that has been studied more frequently. The term “super obesity” has been used variably, but defined often as weighing 150 pounds or more than ideal body weight or having a BMI ≥50kg/m. (6)

Herein we present a case of a patient with a BMI of 100kg/m² admitted with uncontrolled pain due to large necrotic skin ulcers from nonuremic calciphylaxis. Through this case, we review the limitations of data regarding pharmacologic properties for those with super obesity, and provide palliative medicine providers with a framework for such management.

A 28-year-old Caucasian male was evaluated for worsening pain from large skin wounds. His past medical history consisted of super obesity (314kg; 177cm; BMI 100.2kg/m²) and its sequelae—biventricular systolic heart failure; chronic hypoxic and hypercapnic respiratory failure secondary to obstructive sleep apnea and obesity-hypoventilation syndrome managed with nightly continuous positive airway pressure (CPAP); recurrent venous thromboembolism on warfarin; and depression. During the 3 months prior to presentation, the patient fell twice leading to hospitalizations. Deconditioning led to a 71kg weight loss, which likely included both muscle and adipose tissue. The patient developed palpable intertriginous subcutaneous nodules, which subsequently erupted into foul-smelling ulcers that were minimally responsive to prolonged courses of parenteral antibiotics. Palliative care was consulted early during the admission due to exquisitely painful ulcerations in his intertriginous areas and flank (Figure 1).

The patient struggled with obesity since childhood and several of his relatives had obesity. His heaviest weight was 385kg and despite referral for bariatric surgery, he was considered to have a high perioperative risk. The patient had several obesity-related complications including prolonged hospital courses requiring intensive care unit (ICU) care. He had a high school level education and was on disability due to limited mobility and health issues. He lived with his mother who assisted him with toileting, bathing and dressing.

The interdisciplinary team comprised of specialists in wound care, surgery, dermatology, anesthesia, pharmacy, respiratory therapy, palliative medicine, and nursing, provided pain management while undergoing aggressive wound care. A multimodal pain management approach was implemented using duloxetine, pregabalin, acetaminophen, and topical morphine and lidocaine/amitriptyline/ketamine creams, the latter of which were applied to the open wounds. Opioids requirements exceeded 1000 oral morphine equivalents/day. He underwent twice daily bedside dressing changes and surface debridement with conscious sedation consisting of intravenous fentanyl and sublingual ketamine (dosed on ideal body weight), as well as weekly deep surgical debridement. CPAP was used with bedside procedures and postoperatively. Despite multimodal therapy, the patient continued to experience agonizing pain, which limited wound care and resulted in further necrosis and superinfection.

Though initial goals focused on life prolongation and improved pain control, growing concerns about airway protection and reduced respiratory reserve arose, which limited further analgesic titration. Additionally, the patient experienced difficult intubations and hemodynamic instability intraoperatively with debridement.

In line with his goals, the patient transferred to the medical ICU and embarked on a time-limited trial of tracheostomy placement with ventilator support and twice-weekly deep surgical debridement. Baseline analgesia included a continuous fentanyl infusion and patient-controlled boluses for incident pain. Pain with bedside debridement was managed with periprocedural propofol and frequent fentanyl boluses. Previous non-opioid adjuvants were continued. Continuous intravenous ketamine was resumed, this time being dosed on total body weight. Benzodiazepines provided anxiolysis and mitigation of psychotropic effects of ketamine. Nursing used the Richmond Agitation Sedation Score goal of −1 (drowsy) as a target for titrating analgesics. (7) With this improved regimen, the patient’s pain was more optimally controlled using only one-fourth of the total daily opioid dose that he required previously. Regional and neuroaxial techniques were considered but contraindicated due to body habitus, wounds at multiple levels, infection risk, and need for anticoagulation.

Despite aggressive wound care, existing wounds deteriorated and new ones appeared. More intensive wound debridement was required though the multidisciplinary team questioned if this was warranted because the wounds were unlikely curable in this situation. Goals of care were revisited by the interdisciplinary team and the patient requested to be transitioned to a comfort-directed approach after learning there was a dismal chance of the wounds healing. Dressing changes were minimized with a focus on odor control and comfort, and the patient was enrolled in home hospice—using Bi-level Positive Airway Pressure support, parenteral hydromorphone via a battery operated, and sublingual ketamine to facilitate hospital discharge. The patient died comfortably at home five days later.

We present a case regarding the challenges experienced by the interdisciplinary team in managing pain in a patient with super obesity. The patient’s pain management created a therapeutic dilemma because of unpredictable pharmacokinetics, unreliable weight-based dosing, risk of airway compromise and an existential contribution to suffering. Understanding the impact of body adiposity on pharmacokinetics and pharmacodynamics is necessary to ensure safe, effective pharmacotherapy. Interdisciplinary team input is required.

Several direct, but not readily available, methodologies exist to measure directly an individual’s body composition (e.g. underwater weighing, skinfold measurement, bioelectrical impedance analysis, dual-energy x-ray absorptiometry, computed tomography, or magnetic resonance imaging). As a result, several indirect measures have been developed and used in pharmacology literature and clinical studies (8). See Table 1 for an overview of indirect measurements relying on height, weight, and sex. A major limitation of these indirect anthropometric measures is that they fail to distinguish lean from fat mass. (9, 10) Clinicians need guidance regarding which measures of body mass are most appropriate when calculating drug dosage.

The three key pharmacokinetic measures that are altered in those with obesity include volume of distribution (V_d), drug clearance (CL) and elimination half-life (t_½) (see Table 2) (14) Individuals with obesity have increased splanchnic blood flow, which would be expected to decrease drug bioavailability. (11) However, studies have shown that the bioavailability of drugs with substantial hepatic extraction is not significantly different between obese and lean individuals suggesting that drug absorption and bioavailability do not appear to be altered in obese individuals. (12,13)