Endocrine and Electrolyte Disorders

Preoperative Evaluation

Obesity and its complications present major challenges for the anesthesiologist. For the morbidly obese patient, the main concern for the anesthesiologist is the airway and the cardiopulmonary system. Abundant soft tissue in the upper airway makes the obese patient more susceptible to obstructive sleep apnea and the development of hypoxemia and hypercapnia. Obesity also significantly increases the risk of a difficult tracheal intubation.

Morbid obesity is the most common risk factor for obstructive sleep apnea (OSA). Every increase in BMI of two units increases the likelihood of coexisting OSA by 4%. The prevalence of OSA is 3% to 25% in morbidly obese men and 40% to 78% in morbidly obese women, as opposed to 2% in non-obese women and 4% in non-obese men in the general US population.

It is difficult to predict the presence of OSA based solely on a clinical examination. The definitive diagnostic test for OSA is polysomnography. It is, however, impractical to screen all suspected OSA patients with polysomnography and this has led to the development of clinical predictive tools.

A good example is the STOP-BANG questionnaire developed by Chung et al., which has been shown to have consistently high sensitivity for detecting OSA at different severity levels (84% in mild OSA or above, 93% in moderate or above, and 100% in severe). It consists of questions on Snoring, Tiredness, Observed apnea, and high blood Pressure and is combined with BMI > 35, Age > 50, Neck circumference > 40 cm, and male Gender. Like many screening tools, the high sensitivity of the STOP-BANG score allows users to rule out moderate to severe OSA if the scoring tool ranks them as low risk, i.e., the negative predictive value is good.

A subgroup of obese patients are susceptible to a syndrome called the obesity-hypoventilation syndrome (OHS). This is characterized by chronic daytime hypoventilation and chronic daytime hypoxemia (PO ₂ < 65 mmHg) and is easily detected by using room air pulse-oximetry. Sustained hypercapnia (PCO ₂ > 45 mmHg) in an obese patient without significant chronic obstructive pulmonary disease (COPD) is also diagnostic for this syndrome. These patients often have BMI > 40 kg/m and the likelihood of OHS increases as the BMI increases. The underlying pathophysiology of this syndrome is unclear and patients on the extreme end of this spectrum who have signs of cor pulmonale are called “Pickwickian.” Pickwickian conditions are associated with increased perioperative morbidity and mortality and these patients may require more extensive preoperative testing and postoperative management.

Because most clinically severe obese patients do not undergo polysomnographic testing, the diagnosis and severity of OSA in a preoperative patient are most commonly gleaned from patient history. For example, reports of constant snoring, interrupted breathing during sleep, morning headache, and daytime somnolence may be indicative of OSA. Systemic hypertension, a BMI > 35, and a neck circumference > 40 to 42 cm at the cricoid cartilage are consistent with the diagnosis of OSA. At present polysomnographic testing is indicated in severely obese patients who continually snore, have daytime somnolence, or have observed periods of interrupted breathing during sleep. Unfortunately, there are no studies to suggest that this approach is correct. In the setting of morbid obesity and OSA without symptoms or signs of underlying pulmonary pathology, tests for room air, blood gases, and pulmonary function have no predictive value in optimizing postoperative outcomes in severely obese patients. Fig. 40.2 presents an algorithm providing guidance on the preoperative evaluation of patients with morbid obesity.

Treatment with Noninvasive Ventilation

Continuous positive airway pressure (CPAP) can reduce or eliminate signs of sleep apnea. To be successful, the use of CPAP requires experienced respiratory care practitioners and patient cooperation. Hence, it is not surprising that use of CPAP results in failure postoperatively because it is often performed in sleepy and uncooperative patients who have not been formally diagnosed with OSA. In addition, it is also provided by practitioners who are not skilled in CPAP titration. It is important to point out that patients require a period of adaptation to the mask and device and not all patients can tolerate this treatment.

The amount of CPAP required varies depending upon whether the sleep disorder involves rapid eye movement (REM) or non-rapid eye movement (NREM) sleep. For example, a CPAP level that eliminates obstructive and hypoxic symptomology during naps may not be effective for nighttime sleep when REM occurs. Unfortunately, compliance with CPAP is in the range of 50% to 80%. Therefore, it is important for the anesthesiologist to make inquiries of each patient on an individual basis regarding the use of their device.

The use of CPAP to reduce complications associated with OSA has recently come into question with the publication of a large randomized controlled trial that did not demonstrate any benefit to CPAP therapy on reducing the rate of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack.

In the preoperative setting it remains unclear whether surgery should be delayed to optimize airway status and oxygenation with CPAP therapy. One study failed to observe any major postoperative respiratory complications in 14 patients treated with nasal CPAP for a period of 3 weeks before surgery. However, in addition to a small sample size this study suffered from the lack of a control group. Therefore, it could not be determined whether these complications would have occurred without the intervention. Other studies have shown that 3 weeks of CPAP therapy before bariatric surgery improved the left ventricular ejection fraction and afterload in patients with severe obesity and heart failure. Eight weeks of preoperative CPAP may be necessary to treat hypertension (HTN) secondary to OSA. In the postoperative setting, one study revealed that CPAP used on the first night after surgery failed to improve oxygenation. The authors believed that this may have been because the REM rebound does not occur until several days after surgery.

Bilateral positive airway pressure (BiPAP) provides positive pressure to the airway during both inspiration and expiration. With this modality spontaneous ventilation is further assisted with increases in airway pressure and flow. BiPAP may have its greatest use in patients who require a significant amount of CPAP or in those who have a severe underlying airway disease such as COPD. The effectiveness of BiPAP in the general sleep apnea population remains unknown.

Cardiovascular Complications of Obesity

Morbid obesity is associated with a higher frequency of cardiovascular disease, including essential hypertension, pulmonary hypertension, left ventricular hypertrophy, congestive heart failure, and ischemic heart disease. Therefore, many patients with morbid obesity will require a thorough cardiac workup. Preoperative patients can be assigned to a risk group based primarily on history and physical examination and the extent of surgery as per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines.

Cardiac output must increase 0.01 L/min to perfuse each kilogram of adipose tissue adequately. Not surprisingly, obese patients often have hypertension, which can lead to cardiomegaly and left ventricular failure. The mechanism for the development of hypertension may be caused by repeated episodes of desaturation and sleep arousals resulting in the activation of the sympathetic nervous system. Although treatment of sleep apnea may result in improvement of HTN, most often treatment cannot be initiated in time for the planned surgery. Treatment of hypertension should be based on current recommended guidelines for patients without sleep apnea.

The association between obesity, sleep apnea, and atherosclerotic cardiovascular disease remains incompletely understood. Episodes of myocardial ischemia are not temporally related to apneic episodes despite sleep studies demonstrating myocardial ischemia in high risk individuals. Myocardial ischemia in this setting could be caused by increased activation of the sympathetic nervous system, resulting in increased myocardial work and increased oxygen demand. Oxygen demand can easily outstrip delivery in this setting because of hemoglobin desaturation. OSA also predisposes patients to congestive heart failure, arrhythmias, and diastolic heart dysfunction.

Chronic daytime hypoxemia can also result in pulmonary hypertension, right ventricular hypertrophy, or right ventricular failure. Anesthesiologists should consider the use of echocardiography to evaluate right heart failure or pulmonary hypertension in selected patients with clinically severe obesity and OSA. However, data are lacking to support the widespread use of this modality at this time.

Deep Vein Thrombosis

Obesity is also an independent risk factor for deep vein thrombosis (DVT) and pulmonary embolus. The estimated incidence of DVT and pulmonary embolism in the postoperative period after bariatric surgery is 2.6% and 0.95% respectively. Venous emboli migrating to the pulmonary circulation is a significant contributor to the 1% to 2% 30-day mortality after bariatric surgery. Most mortality in the 30-day period after bariatric surgery is a result of pulmonary embolism, and this cause of mortality is threefold higher than anastomotic leak and subsequent sepsis. Unfractionated heparin in a dosage of 5000 units administered subcutaneously before surgery and then two times a day until the patient is ambulatory has been shown to reduce the risk of DVT. Enoxaparin in a dosage of 40 mg twice a day has also been shown to decrease the incidence of complications arising from postoperative DVT.

Intraoperative Concerns

In obese patients, the expiratory reserve volume (ERV) and functional residual capacity are reduced to 60% and 80% of normal respectively. ERV is the primary source of oxygen reserve during apnea. Decreased apneic reserve and possibility of difficult mask ventilation has led some to suggest that awake intubation is the safest way to secure the airway in severely obese patients, indicating the potential for difficult intubation. Because of the higher risk of aspiration in the severely obese patient, most practitioners perform a rapid sequence induction to secure the airway, but there is little data to support this practice.

It has been shown that drugs used for analgesia and neuromuscular blockade have increased volume of distribution and prolonged elimination times in severely obese patients. In one study involving eight obese patients (mean weight 94 kg), the elimination half-life of sufentanil was 208 minutes versus 135 minutes for eight control patients (mean weight 70 kg). In a study examining twitch recovery times of vecuronium, the twitch recovery time was 38.4 minutes in obese patients (mean weight 93 kg) versus 17.6 minutes for non-obese patients (mean weight 61 kg).

Postoperative Concerns

It is absolutely essential postoperatively that obese patients receive some form of continuous oxygen supplementation and be maintained in the semi-recumbent or upright position. If oxygen therapy alone is insufficient to maintain adequate arterial oxygenation, it is recommended that CPAP or BiPAP therapy be instituted. The issue of postoperative disposition and monitoring of OSA patients is controversial. Although it is known that patients with OSA are at higher risk of complications, there is no evidence that higher levels of postoperative monitoring reduce these risks, and the latest guidelines from the American Society of Anesthesiology do not have specific recommendations for postoperative monitoring of these patients.

Recommendations

Data from well-designed randomized trials are lacking in the perioperative care of morbidly obese patients. In particular, there are no data to suggest that outcomes are improved if coexisting conditions such as OSA are diagnosed and treated prior to surgery. In addition, there are no data to reveal whether the type of anesthetic administered has an impact on perioperative outcomes. We do recommend polysomnographic testing with CPAP titration in selected patients, and more extensive cardiac testing in selected patients prior to surgery. We also recommend that DVT prophylaxis begin prior to anesthetic induction and early ambulation be encouraged in the postoperative period. In addition to oxygen supplementation, a low threshold for initiating non-invasive ventilation in the postoperative period is recommended for patients who are hypoxemic. Fig. 40.3 presents an algorithm that provides guidance on the perioperative airway and disposition planning for patients with clinically significant obesity.

Normal Physiology

The zona fasciculata of the adrenal gland secretes approximately 5 mg/m of cortisol per day. For the average sized person, this means the total normal cortisol production is about 8.5 mg/day. Glucocorticoid receptors are present on many different tissue types and play a key role in homeostasis. Specifically, glucocorticoids are necessary for lipid, carbohydrate, and protein metabolism. Glucocorticoids also facilitate catecholamine production and the maintenance of normal blood pressure and affect cardiovascular homeostasis. In healthy subjects, glucocorticoid secretion has a diurnal variation with peak levels occurring between 4 am and 8 am . The nadir of their secretion is between 2 am and 4 am . Interestingly, this diurnal variation is lost in critically ill patients.

With stressors such as critical illness, trauma, and surgery, the normal physiologic response is an increase in the level of adrenocorticotrophic hormone (ACTH), which stimulates the adrenal gland to secrete cortisol. However, there is considerable interindividual variation in the HPA response to these stresses. Some of the variation is thought to be the effect of anesthetics, endogenous and exogenous opioids, age, and sleep. Of particular interest is emerging data suggesting that a significant proportion of opioid treated chronic pain patients display a degree of adrenal suppression. Furthermore, the amount of glucocorticoid secreted depends on the amount of surgical stress. Minor surgical procedures result in an adrenal secretion of approximately 50 mg of cortisol per day, whereas major surgical procedures produce between 75 and 150 mg of cortisol per day. To put these levels in perspective, patients with Cushing syndrome secrete an average of 36 mg/day of cortisol. The daily production of cortisol during periods of stress seldom exceeds 200 mg/day in normal subjects. This suggests that this is the maximum dosage that should be administered to patients thought to be at risk of postoperative adrenal insufficiency.

Effect of Chronic Steroid Supplementation on the HPA Axis

Adrenal insufficiency (AI) can be classified as either primary (resulting from the destruction of the adrenal gland by tumor, infection, or hemorrhage), secondary (resulting from pituitary dysfunction), or tertiary (resulting from the therapeutic administration of glucocorticoids). By far, the most common cause of AI is tertiary. Exogenous administration of glucocorticoids results in the inhibition of the hypothalamic and pituitary glands, which results in the atrophy of the adrenal gland over time. Precisely how long it takes for the adrenal gland to recover its function from the exogenous administration of glucocorticoids is the subject of much debate. Studies have shown that the adrenal gland can take as little as 2 to 5 days to recover its normal function or as long as 9 months to a year.

Diagnosis of Adrenal Insufficiency

The diagnosis of tertiary AI in a postoperative patient is difficult and subject to error. Both clinical and physical examination findings need to be supplemented with biochemical testing to confirm the diagnosis. The typical history of fatigue, anorexia, postural hypotension, and weight loss seen in adrenally insufficient patients in the outpatient setting is not relevant in the postoperative state. Surgical patients most often present with an Addisonian crisis that includes fever and hypotension unresponsive to fluid or vasopressor support. The diagnosis is thus confounded by typical postoperative mimics such as hypovolemic shock or sepsis.

Biochemically, the classic findings of adrenal insufficiency include hyponatremia and hyperkalemia. Hyponatremia might be masked by the administration of perioperative fluids. Hyperkalemia is often not present because of intact mineralocorticoid secretion thanks to the renin-angiotensin-aldosterone system. The limitations of the physical examination and baseline biochemical data therefore argue for a more focused interrogation of the HPA axis either with an ACTH stimulation test or with a random cortisol level.

Determining an adequate cortisol response in a postoperative patient suspected of having adrenal disease is made challenging by the previously mentioned interindividual and procedural variability in cortisol levels. Ideally, a threshold cortisol level could be defined, below which the diagnosis of adrenal insufficiency could be made with a high degree of certainty, and therapeutic replacement could be initiated. There are currently no clear consensus values used in the diagnosis of postoperative or critical illness related adrenal insufficiency. A random cortisol value of < 10 μg/dL has appeared in older guidelines as a value below which a diagnosis of adrenal insufficiency can be made. Patients whose cortisol level is above 34 μg/dL are unlikely to have AI and need not be treated.

Further testing of the HPA axis can be accomplished with the ACTH stimulation test. This involves the administration of 250 μg of intravenous cosyntropin (a synthetic ACTH analog) and the measurement of plasma cortisol levels at baseline and at 30 and 60 minutes after administration. Current guidelines suggest that a cortisol value of less than 18 μg/dL (assay specific) recorded at any of the time points are needed to confirm adrenal insufficiency. These guidelines, however, are written for the diagnosis of primary adrenal insufficiency and not AI related to critical illness or perioperative stress.

Unfortunately, anesthesiologists often do not have the luxury of waiting for the results of specialized biochemical tests when faced with a hypotensive patient in the operating room or the recovery room who might have AI. One management option, should this situation arise, would be to administer 8 mg of dexamethasone to the patient, as this will adequately provide the “stress dose” required without interfering with any subsequent testing of the HPA axis. Concurrently, a random cortisol level should be drawn to check for the presence of AI.

Incidence of Adrenal Insufficiency

The reported incidence of tertiary AI in at risk surgical patients ranges from 0.1 to 1 in 1000. Whether this represents an actual low incidence, under-reporting, or poor recognition of this condition is unclear. Many patients undergo major surgical procedures without perioperative glucocorticoid coverage, or even without their baseline therapeutic dosage, without sequelae. The likely explanation for this is that these patients have normal HPA axis function in response to stress.

A collection of small studies has examined the outcomes of omitting additional corticosteroid administration in times of stress amongst patients who would be considered to have corticosteroid induced impaired HPA axis. Bromberg and colleagues prospectively studied 40 renal transplant patients on long-term steroids for immunosuppression who required hospital admission for surgical procedures or acute illness. Despite no stress doses being administered they found no clinically significant cases of adrenal insufficiency.

Glowniak and Loriaux studied patients taking at least 7.5 mg of glucocorticoid per day who underwent major surgical procedures. There were no cases of clinically significant adrenal insufficiency found in either the treatment (stress dosed) or control arm. In 2012 and 2014 Zaghiyan et al. completed two studies involving steroid-treated patients with inflammatory bowel disease requiring bowel surgery. Based on these two studies they concluded that continuing only daily home dose steroids perioperatively was not more likely to yield additional cases of adrenal insufficiency than if patients were administered stress doses. Further, within these studies patients who had been treated with steroids but were not actively taking them did not display AI features despite no perioperative steroid being given.

Despite this, adrenal crisis remains a rare yet feared and potentially fatal complication in the perioperative period and patients taking exogenous steroids are at risk. In light of the rarity of adrenal insufficiency and the small size of studies refuting the need for stress dose steroids, many practicing anesthesiologists retain a conservative approach.

Identifying patients at risk for adrenal insufficiency

The commonly agreed upon scenarios for which perioperative stress dose steroids are indicated include patients who take > 20 mg prednisone equivalent per day for > 3 weeks or have clinical features of Cushing syndrome. Patients who take less than 5 mg/day prednisone equivalent or who have taken any dose for less than 3 weeks are considered to have intact HPA axes and do not require stress dose steroids. Patients who take topical or inhaled steroids are at extremely low risk of developing tertiary AI.

A number of patient groups fall outside of these categories. Such patients form an intermediate group for whom there is concern for HPA axis suppression but limited, if any, evidence to support the practice of administering stress dose steroids. For these patients the risk of harm with excess steroid is a significant concern. Patients who fall into this group include those who: (1) take between 5 and 20 mg prednisone equivalent per day, (2) have received epidural or intra-articular steroid injections in the past 90 days, and (3) were treated but have stopped corticosteroid use within the past year.

Determining which of these patients, if any, need stress dosing is a topic of much debate. No clear guidelines exist. An attractive and much discussed approach is to perform a 250-μg ACTH stimulation test preoperatively although its use has not been shown to predict accurately which patients will develop tertiary AI. It is also time-consuming and costly, making it frequently impractical in the preoperative setting. An alternative approach is to omit stress dosing for these patients and administer a rescue dose of hydrocortisone only if features of AI develop.