In recent years, obesity has become one of the serious public health problems in many countries. Recent data show that 30% of Americans are obese (Body Mass Index (BMI) 30) and 4 or 9% of Americans are morbidly obese. It is believed that with the improvement of material level, the proportion of obese people among the sick population in China will gradually increase, and the number of obese patients who need to undergo surgical procedures will also increase. Therefore, it is necessary for anesthesiologists to acquire knowledge about obesity in order to provide more scientific medical services to obese patients. In this paper, we will give a preliminary explanation on the pharmacokinetics and anesthesia management of obese patients.
I. Drug metabolism kinetics
Like normal weight patients, the drug distribution in the tissue of obese patients is mainly affected by the plasma protein binding rate, tissue composition and local blood flow. Changes in any of the above factors will change the volume of drug distribution, thus changing the concentration of drugs in the blood. Plasma protein binding rates do not differ significantly in normal weight and obese individuals. In obese patients, there is an increase in both defatted weight and fat weight, but the percentage increase in fat weight is greater than the percentage increase in defatted weight [2]; a simple calculation shows that obese individuals contain more fat and less defatted weight per kilogram of body weight compared to normal weight individuals.
Under normal conditions, blood flow from fat is minimal, accounting for only 5% of cardiac output, while visceral blood flow is 73% and muscle tissue 22% [3]. The blood volume of the body increases with weight, so many obese people have increased cardiac output, and various visceral organs such as brain, liver, and kidney are well perfused due to abundant blood flow [4, 5], which is important for the distribution, action, and metabolism of intravenous and inhaled anesthetics in the body.
Current studies on sedation have focused on isoproterenol. A comparative study with normal weight showed [6] that isoproterenol given according to body weight in obese patients had satisfactory clinical results with constant initial volume of distribution (Vd, in L/kg) and positive correlation of clearance and steady-state volume of distribution with body weight. Steady-state volume of distribution refers to the volume of distribution when isoproterenol acts rapidly on the brain (central compartment in the two-compartment model) after sedation, and then part of it is rapidly cleared by the liver (central compartment) and the other part is bound to adipose tissue (peripheral compartment), and the distribution of the drug between tissues is balanced.
Fentanyl is the opioid currently in common use. One investigator [7] administered continuous infusion of fentanyl based on the patient’s body weight (total body weight, TBW) during prolonged surgical anesthesia in normal weight (BMI ≤ 30) and obese (BMI 30) patients and found that for obese individuals, the amount of fentanyl infusion calculated based on body weight was much greater than the actual amount needed. This led to the derivation of a parameter called pharmacokinetic weight, which ranged from 100 to 108 kg for individuals weighing between 140 and 200 kg. A study comparing the metabolic kinetics of remifentanil in 12 obese individuals and 12 normal weight individuals [8] found that plasma remifentanil concentrations were significantly higher in obese individuals than in normal individuals after a single loading dose, suggesting that remifentanil should be administered according to ideal body weight (IBW) or fat-free body weight (LBW) administration.
The findings are similar for inotropic agents. Especially for hydrophilic inotropes, their volume of distribution will not be large due to their low affinity for fat. Vecuronium bromide given according to body weight (TBW) in obese individuals has a prolonged duration of action, and if given according to ideal body weight (IBW), its volume of distribution, clearance, and elimination half-life are intermediate between normal body weight and obese individuals [9]. The recovery time of myocardial relaxation for rocuronium given to obese individuals according to body weight and ideal body weight was 55 and 22 minutes, respectively (the time taken to recover the intensity of myocardial twitches to 25% of the baseline value with the application of a single current stimulus from a neuromuscular stimulator) [10]. Similar findings were found for cis-atracurium [11]. Therefore, for non-depolarizing myorelaxants, they should be administered according to ideal body weight to prevent prolonged myorelaxant effects.
During the last decade, sevoflurane and desflurane have been gradually used in clinical practice. These two inhalation anesthetics are characterized by low solubility in the blood, rapid absorption, rapid action and rapid excretion. Theoretically, anesthesia with less distribution in fat
gas is more beneficial to obese patients. Several studies have shown that patients awakened fastest with the application of desflurane, followed by sevoflurane and isoflurane [12, 13, 14]. In a trial using desflurane, isoflurane, and isoproterenol as the primary anesthetic maintenance drugs, respectively, it was concluded that patients in the desflurane group awakened fastest [15]. In conclusion, all available anesthetic gases are safe for obese individuals, and desflurane is faster to induce and awaken due to its small blood/gas partition coefficient and fat/blood partition coefficient (0,42 and 27,2, respectively), but it is expensive. Sevoflurane has the advantage of a sweet taste and can be used alone or in combination with laughing gas for inhalation induction. Isoflurane has been used for many years and is safe and inexpensive.
Second, the surgical position
Recently, it has been reported that several morbidly obese people who received gastric bypass surgery in the supine position for 5 hours suffered renal failure and even died because of rhabdomyolysis of the gluteal muscles [16, 17]. Prone, lateral, and truncal positions are challenging for overly obese individuals, especially for prolonged surgery, where the area located below is sometimes unable to withstand the gravitational force above, and compressive necrosis or osteofascial compartment syndrome occurs [18]. Therefore, care should be taken to protect the upper and lower extremities and joints.
III. Intraspinal anesthesia and nerve block
Lumbar anesthesia and epidural anesthesia have been widely used in obese patients in obstetrics and have proven to be feasible and safe. For overly obese patients, the operation can be performed in the sitting position, sometimes requiring special long puncture needles and catheters (such as Braun’s 15 cm epidural puncture needle and 11 or 9 cm lumbar puncture needle). It is important to note that the epidural catheter tends to shift with fat movement [19]. Care should be taken with the amount of local anesthetic in either lumbar or epidural anesthesia, as it is more likely to spread to the head and cause hemodynamic instability compared to normal weight patients [20, 21]. The use of heavy specific gravity fluid is recommended for lumbar anesthesia because of its ease of binding to nerve fibers and ease of controlling the plane of anesthesia. Obese patients undergoing open surgery under general anesthesia have significantly reduced lung volumes, and compound epidural anesthesia and/or postoperative epidural analgesia may reduce the degree of postoperative lung volume reduction [22].
A large sample of 9,000 patients showed increased patient satisfaction with nerve block anesthesia or indwelling catheter postoperative nerve block analgesia for obese patients, but with a corresponding increase in block failure rates and complications [23]. Therefore, the pros and cons should be weighed when considering whether to perform nerve blocks in obese patients.
IV. Intraoperative monitoring
In addition to routine monitoring, some patients need to establish central venous access. Ultrasound-guided puncture placement is helpful for some difficult punctures. Invasive arterial monitoring is feasible when reliable blood pressure readings cannot be obtained by cuff measurement (insufficient cuff width, excessive upper arm fat). Pulmonary artery pressure should also be monitored in critically ill patients such as those with pulmonary hypertension and pulmonary origin heart disease.
V. Laparoscopic gastric bypass surgery for obese patients
There is increasing evidence that surgical bariatric surgery can provide long-term weight loss and reduce complications due to obesity [24]. In the United States, laparoscopic gastric bypass surgery is now widely used. The artificial pneumoperitoneum required for laparoscopic surgery increases intra-abdominal pressure (IAP), which affects the cardiovascular system. When IAP is ≤10 mmHg, vena cava return increases, resulting in increased cardiac output and arterial pressure; higher intra-abdominal pressure prevents vena cava return, resulting in lower cardiac output [25]. Artificial pneumoperitoneum and obesity itself affect the patient’s respiratory mechanics in the perioperative period. One of the serious perioperative problems in obese individuals with reduced functional residual air volume is poor lung expansion [26].
Obese individuals have reduced pulmonary compliance, which is further reduced by artificial pneumoperitoneum, and therefore may require increased ventilation intraoperatively. It was found that post-anesthesia supine pulmonary compliance was 29% lower in morbidly obese patients than in normal weight individuals, and that even the use of double the tidal volume or double the respiratory rate sometimes had difficulty in correcting the poor alveolar-arterial gas gradient [27]. Occasionally, the tracheal tube has been reported to be displaced in the right main bronchus due to head-down position and artificial pneumoperitoneum [28]. Despite these problems, many studies have confirmed that postoperative complications are rare as long as the IAP is <15 mmHg.
For many years, it has been recognized that obese individuals are more prone to hypoxemia after anesthesia than normal weight individuals. The predisposition to decreased oxygen saturation after induction of anesthesia makes a preemptive denitrogenation and oxygenation procedure very important. The compensatory expiratory volume, force spirometry, one-second rate, and functional residual air volume are reduced in overly obese individuals. Changes in respiratory mechanics of the lungs and thorax, such as decreased respiratory compliance, increased respiratory resistance, and impaired oxygenation, are readily observed after mechanical ventilation [32].BMI is an important determinant of respiratory mechanics. As BMI increases, functional residual air volume, pulmonary compliance and oxygenation index decrease. Another cause of postoperative hypoxemia in obese patients is reduced lung volume and imbalanced ventilation-blood flow ratio [33].
Patients should be adequately evaluated preoperatively for difficult intubation, and awake intubation should be considered when mask ventilation is estimated to be difficult. A patient in a head-high position, with the upper body higher than the lower body, has proven to facilitate direct laryngoscopic exposure of the vocal cords [34]. If intubation is unsuccessful, insertion of a laryngeal mask to establish ventilation is an option [35]. Prevention and reduction of lung distension insufficiency during induction and maintenance can improve lung oxygenation. During mask ventilation prior to induction, having the patient inhale 100% oxygen with a positive end-expiratory pressure of 10 cm water column can improve arterial oxygenation immediately after intubation and prolong the time before oxygen saturation drops, gaining time for difficult intubation [36]. The use of a positive end-expiratory pressure of 10 cm water column in the maintenance of anesthesia in overly obese patients promotes alveolar recovery and improves arterial oxygenation [37].