The Morbidly Obese Patient

Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome

Obstructive sleep apnea (OSA) is an obesity-related disorder characterized by upper airway collapse during sleep. Increases in adiposity of upper airway structures leads to reduced airway caliber and reduced pharyngeal muscle tone. ^, Symptoms include snoring and apneic episodes during sleep, daytime sleepiness, and morning headaches. Diagnosis is usually confirmed with polysomnography. Treatment consists of continuous positive airway pressure (CPAP) at night and weight loss. ^,

Obesity hypoventilation syndrome (OHS), or Pickwickian syndrome, occurs when the physiologic changes described in the preceding paragraph lead to increased daytime hypercarbia. The Academy of Sleep Medicine defines OHS as daytime alveolar hypoventilation (Pa co ₂ > 45 when awake and at sea level) in individuals with a BMI greater than 30 when other etiologies of hypercarbia are excluded, such as chronic obstructive pulmonary disease, mechanical respiratory dysfunction such as severe kyphoscoliosis, and neuromuscular disease. ^{, ,} It is also prudent to screen for pharmaceutical and recreational substances that affect respiratory drive such as opioids, sedative-hypnotics, and alcohol. While not all, or even most, patients with OSA will have OHS, 90% of those suffering from OHS also suffer from OSA with as many as 70% with severe OHS (characterized by more than 30 apnea-hypoxia events per hour during sleep). Patients with OHS have increased rates of pulmonary hypertension, congestive heart failure (CHF), acute or chronic hypercapnic respiratory failure, and mortality compared to those with only OSA. One recent study identified 600 patients in a 5-year period with OHS and noted 15% died on the index visit with another 16% dying in the approximately 3-year follow-up period.

The American Thoracic Society recently issued a clinical practice guideline regarding evaluation and treatment of OHS. They suggest that patients with sleep disordered breathing but a low/moderate (<20%) pretest probability of OHS should undergo screening with serum bicarbonate levels. Patients with bicarbonate levels over 27 mmol/L or those with a high pretest probability of OHS should undergo confirmatory testing of arterial carbon dioxide levels. They also recommend immediate treatment with noninvasive ventilation and suggest evaluation for bariatric surgery.

Antibiotics

There is limited data on beta-lactam and cephalosporin use in obesity, but several trials have illustrated lower than normal drug concentrations and cure rates in obese patients when standard dosing is utilized. Until more data are available, we recommend initial dosing at the upper limit of the recommended dose and suggest extended infusion times ( Table 184.4 ).

Fluoroquinolones also have very limited pharmacokinetic data in the setting of obesity. There are insufficient data to provide clear recommendations for ciprofloxacin. Levofloxacin 750 mg/day has been shown to be effective against gram-negative infections in small studies of obese patients with preserved renal function, but further data is required before firm recommendations can be made for fluoroquinolones. Therefore, we recommend usual dosing.

Vancomycin has both increased V _d and Cl in obese patients and obese patients have been found to have lower vancomycin troughs. The large V _d necessitates a loading dose recommended at 20 to 25 mg/kg TBW; doses >4 g/day are associated with vancomycin-induced nephrotoxicity. Variable Cl in conjunction with the large V _d makes maintenance dosing difficult and it is prudent to individualize subsequent doses to peak and trough levels so as to achieve therapeutic levels but avoid nephrotoxicity. ^,

Linezolid is noted to have subtherapeutic levels in obese patients, but data have not illustrated worse clinical outcomes. Expert recommendations are mixed at this time and there are insufficient data to give clear guidelines regarding linezolid dosing in obese patients; therefore, we recommend usual dosing. ^,

Aminoglycosides are hydrophilic but do have an increased V _d in obese patients, suggesting that the drug does distribute into fat tissue but not to nearly the same concentrations as other tissues. Limited evidence suggests dosing by ABW with a correction factor of 0.4 for the loading dose with maintenance dosing individualized for the patient. ^,

Sedatives and Induction Agents

Recent studies have demonstrated that both obese and non-obese children and adults often receive incorrect anesthetic and paralytic medications, with one investigation reporting only 75% of obese patients receiving an appropriate dose of etomidate and 60% being administered the correct dose of succinylcholine. ^, Propofol is highly lipophilic; in fact, one of the great advantages of this drug, its short duration of action, is not due to metabolism but rather to rapid redistribution into muscle and fat. Historically there has been controversy regarding the appropriate scaler for propofol, but recent research has suggested that using ABW with a correction factor of 0.4 results in successful sedation ( Table 184.5 ). ^{, ,} Although etomidate is ubiquitous in the ED, little research has been performed regarding optimal dosing in obese patients with some experts recommending TBW and others reduced doses. ^, One recent study did demonstrate IBW resulted in successful sedation, but currently there is insufficient evidence to give a strong recommendation regarding which scaler should be used. At this time we suggest using TBW to dose etomidate. Similarly, there is a paucity of data for ketamine in the obese patient; however, given its large V _d , most experts suggest reducing from TBW with some suggesting IBW and others LBW. We suggest utilizing LBW. ^,

Neuromuscular Blocking Agents

Succinylcholine, a depolarizing neuromuscular blocking agent, is cleared via breakdown by plasma cholinesterase (PCE). Obese patients have increased levels of PCE proportional to total body weight and therefore succinylcholine (1.5 mg/kg IV) should be dosed by TBW. ^, The non-depolarizing neuromuscular blocking agents most commonly used in the ED, vecuronium and rocuronium, have both been shown to have prolonged duration of action when administered by total body weight. ^, One recent trial illustrated that using 0.6 mg/kg IBW of rocuronium did not result in slower time of onset than when using higher doses in obese patients. However, given that the only complication of higher doses of non-depolarizing agents is prolonged duration of action and underdosing risks suboptimal intubating conditions, we recommend using TBW for these medications. Sugammadex rapidly reverses paralysis due to the non-depolarizing neuromuscular blocking agents (rocuronium and vecuronium). Recent research suggests the possibility of using IBW; however, as most trials investigating sugammadex are conducted in the operating room at the end of surgical cases as opposed to situations where it would likely be utilized in the ED, the end points of these trials allow for a time to onset that would be inappropriate in the emergency department. ^{, ,}