A Clinical Guide to Pediatric Weight Management and Obesity, 1st Edition
Acute Obesity-Related Emergencies
Obesity is a chronic disease; however, obesity-related life-threatening emergencies can occur and must be considered as part of the obesity spectrum of care. Both hyperglycemic hyperosmolar state (HHS) and diabetic ketoacidosis (DKA) can be life-threatening presentations of type 2 diabetes. Pulmonary emboli and cardiomyopathy of obesity are rare but emergent cardiovascular complications of obesity. Each of these complications both illustrates the severity of obesity and highlights aspects of pathophysiology that can occur in the pediatric age group.
Hyperglycemic Hyperosmolar State
State of the Problem
Cases of HHS have now been reported in adolescents with type 2 diabetes. Morales and Rosenbloom (1) described seven obese African American teenagers who were considered to have died of DKA. On review, these adolescents were found instead to have had HHS.
Hyperglycemia in the absence of ketosis can occur in diabetic patients with type 2 diabetes. Relative insulin deficiency develops in the obese patient as insulin resistance increases and beta cell function declines. Loss of suppression of hepatic glucose production occurs, with attendant hyperglycemia. However, enough insulin function may remain to allow suppression of ketosis and lipolysis (2). The initial event in HHS is glycosuric diuresis with glycosuria, impeding the concentrating ability of the kidney and increasing water loss (3). The decreased glomerular filtration rate causes glucose to increase with excess water loss over the sodium loss, leading to hyperosmolarity. Insulin is present but, because of greater insulin resistance, cannot reduce the serum glucose (4). It is important to be alert for signs and symptoms of type 2 diabetes in obese children and adolescents and to be able to recognize HHS on presentation.
A review of 190 children and adolescents with type 2 diabetes presenting over a 5-year period found the frequency of HHS to be 3.7%. All seven patients diagnosed with HHS were African American children with an average age of 13.3 years (10–16 years) whose initial presentation with type 2 diabetes was with an episode of HHS. The mean body mass index (BMI) was 32.7 kg/m2. The mean serum osmolality was 393 mOsm/L, and the mean blood glucose was 1,604 mg/dL. One patient died (5). Death in HHS has been reported to occur from hypovolemic shock and rhabdomyolysis with multisystem organ failure (6). An adolescent patient presenting with HHS has been reported dying on the sixth day of hospitalization from a massive pulmonary embolism (PE) (7).
Patients have presented to medical care with symptoms of vomiting, abdominal pain, dizziness, weakness, polyuria/polydipsia, weight loss, and diarrhea prior to death, which may not be linked to the presentation of type 2 diabetes unless there is a high index of suspicion.
Diagnostic criteria for HHS include the following:
- Plasma glucose greater than 600 mg/dL
- Serum carbon dioxide greater than 15 mmol/L
- Small or absent ketonuria
- Serum osmolality greater than 320 mOsm/kg
- Stupor or coma (1,8)
Mortality rates of 14% in adolescents presenting with HHS have been reported (5). A fatal malignant hyperthermia syndrome with rhabdomyolysis and hyperpyrexia has been described in obese adolescent males with HHS (9).
State of the Problem
Type 2 diabetes can present with DKA. If basal insulin sensitivity is low, as it is in obese patients with insulin resistance, there is increasing susceptibility to relative insulin deficiency.
The cause of DKA in type 2 diabetes is hyperglycemia with relative insulin deficiency, producing increased lipolysis and release of free fatty acids, as well as ketonemia and ketonuria (Fig. 15.1).
In a series of patients aged 9 to 18 years presenting with DKA, there was a 13% prevalence of patients with type 2 diabetes (10). DKA has been reported in a
13-year-old boy with Prader-Willi syndrome and nonalcoholic steatohepatitis (NASH) 1 month after beginning growth hormone therapy. The hyperglycemia resolved 2 months after growth hormone therapy discontinuation, but the patient developed type 2 diabetes 6 months later with weight gain (11).
FIG. 15.1. Diabetic ketoacidosis.
The pathophysiology of DKA results from relative insulin deficiency and elevated levels of counter-regulatory hormones. When insulin is deficient, increased glucagon, catecholamines, and cortisol stimulate hepatic glucose production by increasing glycogenolysis and gluconeogenesis. The rise in cortisol increases protein breakdown and the availability of amino acid precursors for gluconeogenesis. Low insulin and high catecholamine levels reduce peripheral uptake of glucose. These processes result in hyperglycemia, which causes glycosuria, osmotic diuresis and dehydration, and decreased renal perfusion.
In DKA, hormone-sensitive lipase is activated in a state of low insulin availability. Elevated catecholamines, cortisol, and growth hormone cause the breaking down of triglyceride and the release of free fatty acids. Free fatty acids are converted to ketones in the liver and are released, causing ketonemia. An increase in glucagon causes increases in acyl coenzyme A, a substrate for synthesis of hydroxybutyric acid and acetoacetic acid, the main contributors to acidosis (12).
Diagnostic criteria for DKA are blood glucose greater than 11 mmol/L (normal 4.2–6.4 mmol/L), venous pH less than 7.3 (normal 7.35–7.45), and/or serum bicarbonate less than 15 mmol/L. There is associated glycosuria, ketonuria, and ketonemia (12,13).
Diagnosis, monitoring, and treatment have recently been reviewed (13). Success of treatment depends on correction of dehydration to restore renal perfusion and to correct hyperglycemia, ketoacidosis, and electrolyte deficits (12,13).
State of the Problem
Pulmonary embolism is more common in adult obese patients than in the pediatric age group. Symptoms of PE include the following:
- Chest pain
In a study of PE in adolescents, adolescents were more likely to have a normal chest radiograph, less likely to be tachypneic, and less likely to have an abnormal chest examination than adults. PE should be considered for “any adolescent who presents with unexplained pleuritic chest pain, dyspnea, or hypoxemia, particularly in the presence of risk factors or supportive exam findings” (14).
The incidence of PE increases with age in adults. In adults, antithrombotic drugs are the mainstay of prevention and treatment (15). A review of National Hospital Survey Data showed a relative risk of deep venous thrombosis of 2.5 in obese compared with normal weight adults and a relative risk of developing a PE of 2.21. Females and patients younger than 40 years were at somewhat greater risk (16).
Obesity and the associated metabolic disorders may increase the risk of venous thrombosis by altering the balance between thrombotic and thrombolytic activity. Ob/ob leptin-deficient mice have a decreased thrombotic response and experience a lower rate of venous thrombosis and PE after injury than normal mice (17). Sixty percent of normal mice pretreated with a leptin-neutralizing antibody survived otherwise lethal venous thrombosis and PE. Obese humans have an excess of leptin and leptin resistance, which may play a role in their increased risk of thrombosis (17).
The major factors contributing to PE in adults are as follows (18):
- Heart disease
- Acute paraplegia
- Prior history of venous thromboembolism
- Use of oral contraceptives
- Inflammatory bowel disease
- Coagulation disorders (19)
- Obstructive sleep apnea syndrome (19)
In adults, risk of deep vein thrombosis is doubled in obese patients (20). Both obesity and trauma are risk factors for deep vein thrombosis and PE and prophylactic anticoagulation has been recommended as treatment for adult trauma patients who are obese (21).
PE can be a complication of bariatric surgery and the most common cause of unexpected death in the morbidly obese patient (22). PE has been reported in adolescents following gastric bypass surgery (23). PE can also be a complication of orthopedic surgery. Adults undergoing hip fracture surgery who were receiving prophylaxis had mortality and fatal PE rates of 3.2% (2.8% to 3.6%) and 0.30% (0% to 0.61%) (24). Prevention of deep venous thrombosis and PE includes the reduction of obesity and inactivity and the cessation of cigarette smoking.
Cardiomyopathy of Obesity
State of the Problem
BMI is positively correlated with increased right-sided heart pressures, cardiac output, pulmonary vascular resistance index, and systolic blood pressure in adults with congestive heart failure. One study found that obese patients had higher right-sided heart pressures, cardiac output, and pulmonary vascular resistance index when compared with a group of lean patients having a similar degree of cardiomyopathy (25).
The cardiomyopathy of obesity is thought to result from high metabolic activity of excessive fat, which increases total blood volume and cardiac output, resulting in left ventricular dysfunction. Left ventricular wall stress increases, causing dilation and compensatory left ventricular hypertrophy and diastolic dysfunction, which results in heart failure (Fig. 15.2). Right ventricular dysfunction can be exacerbated by pulmonary hypertension due to upper airway obstruction (26).
In obese Zucker mice, excess lipid accumulates in the myocardium, which may cause a “lipotoxic” cardiomyopathy (27). Recent imaging studies in humans have shown that myocardial lipid content increases with the degree of adiposity (28).
FIG. 15.2. A 17-year-old patient with biventricular cardiac failure and cardiomyopathy of obesity.
Issues in Intensive care of the Obese Child and Adolescent
As the epidemic of obesity and morbid obesity increases in the pediatric age group, obesity-related comorbidities are becoming more common and need to be identified in any hospitalized obese patient (Table 15.1). Signs and symptoms suggestive of these comorbidities should be promptly investigated.
Issues related to proper-sized equipment and accurate drug dosing should be addressed on an individual basis for each obese patient.
Pulmonary mechanics are altered by obesity.
Chest wall compliance is reduced, and full anterior excursion is hampered (29). Forced expiratory reserve volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FEV25-75), and diffusing capacity for carbon monoxide have all been found to be reduced in obese children (30).
Upper airway obstruction should be identified in any hospitalized obese patient with symptoms of snoring, apnea, history of orthopnea, daytime tiredness, poor school performance or executive functioning, or family history of upper airway obstruction. Bilevel airway pressure (BiPAP) or continuous positive airway pressure
(CPAP) should be prescribed if used at home; a sleep study should be performed if symptoms are present prior to elective hospitalization so proper respiratory support can be provided. In a series of 14 obese patients undergoing tonsilloadenoidectomy for obstructive sleep apnea, 2 patients required overnight BiPAP for oxygen desaturation, 1 patient required prolonged intubation, and 3 patients required supplemental oxygen (31). Prior history of asthma, asthma exacerbations, and seriousness of intervention needed should be ascertained in the obese child admitted to the hospital. Hospitalization may present an opportunity to optimize asthma therapy in this population. Restrictive lung disease is a component of the respiratory derangements in obesity, and because of this, postoperative attention to pulmonary toilet may be especially important in these patients.
TABLE 15.1. Obesity-related comorbidities
Respiratory issues need to be anticipated in morbidly obese patients, with adequate respiratory support provided in the immediate postoperative period (32).
Severe illness may exacerbate hyperglycemia. In adults in an intensive care unit, hyperglycemia was common and associated with adequacy of glucose regulation prior to the acute hospitalization. This relationship with prior glucose control held true even in nondiabetic patients. Treatment with steroids, norepinephrine, and carbohydrate administration contributed to hyperglycemia (33).
Adult surgical patients in a surgical intensive care setting receiving mechanical ventilation were randomized to receive usual care or intensive control of blood glucose
levels between 80 and 110 mg/dL. Mortality in the intensive control group was half (4.6% vs. 8.0%) of that in the usual care group. Improved outcome was due to decreased incidence of sepsis in patients with longer term stays in the intensive care unit. Intensive insulin therapy also prevented acute renal failure (34).
In another study, morbidly obese (BMI >40 kg/m2) and normal weight adults admitted to an intensive care unit were compared regarding outcomes. Sixty-one percent of the obese patients required mechanical ventilation versus 46% of normal weight patients. Length of mechanical ventilation and stay in the intensive care unit was increased, and mortality was almost double that of the normal weight patients (30% vs. 17%). Multiorgan failure, respiratory failure, and left ventricular dysfunction were associated with the increased mortality (35). Children and adolescents with morbid obesity will have the normal range of infections, trauma, and metabolic diseases expected in a pediatric population. Few studies have been performed that assess the impact of obesity on children in the hospital and intensive care unit.
Individualized assessment and planning are critical for any obese child undergoing hospitalization.
- Morales AE, Rosenbloom AL. Death caused by hyperglycemic hyperosmolar state at the onset of type 2 diabetes. J Pediatr.2004;144(2):270–273.
- Glaser N. Pediatric diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Clin North Am.2005;52(6):1611–1635.
- Wachtel T, Stillman R, Lamberton P. Predisposing factors of diabetic hyperosmolar state. Arch Intern Med.1987;147(3):499–501.
- Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician.2005; 71(9): 1723–1730.
- Fourtner SH, Weinzimer SA, Levitt Katz LE. Hyperglycemic hyperosmolar non-ketotic syndrome in children with type 2 diabetes.Pediatr Diabetes.2005;6(3):129–135.
- Carchman RM, Dechert-Zeger M, Calikogluc AS, Hasrris BD. A new challenge in pediatric obesity; pediatric hyperglycemic hyperosmolar syndrome. Pediatr Crit Care Med.2005;6(1):20–24.
- Bhowmick SK, Levens KL, Rettig KR. Hyperosmolar hyperglycemic crisis: an acute life-threatening event in children and adolescents with type 2 diabetes mellitus. Endocr Pract.2005;11(1):23–29.
- Rubin HM, Kramer R, Drash A. Hyperosmolarity complicating diabetes mellitus in childhood. J Pediatr.1969:74:177–186.
- Hollander A, Olney R, Blackett P, Marshall BA. Fatal malignant hyperthermia like syndrome with rhabdomyolysis complicating the presentation of diabetes mellitus in adolescent males. Pediatrics.2003;111(6Pt1):1447–1452.
- Sapru A, Gitelman SE, Bhatia SK, Bubin RF, Newman TB, Flori H. Prevalence and characteristics of type 2 diabetes mellitus in 9-18 year old children with diabetic ketoacidosis. J Pediatr Endocrinol Metab.2005;18(9):865–872.
- Yigit S, Estrada E, Hyams J, Rosengren J. Diabetic ketoacidosis secondary to growth hormone treatment in a boy with Prader-Willi syndrome and steatohepatitis. J Pediatr Endocrinol.2004;17(3):361–364.
- Chiasson JL, Aris-Jilwan N, Belanger R, Bertrand S. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. CMAJ.2003;168(7):1–19.
- Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Glaser NS, Hanas R, Hintz RL, Levitsky LL, Savage MO, Tasker RC, Wolfsdorf JI. European Society for Pediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics.2004;113:e133–e140.
- Bernstein D, Coupey S, Schonberg K. Pulmonary embolism in adolescents. Am J Dis Child.1986;140(7):667–671.
- Motsch J, Walther A, Bock M, Bottiger BW. Update in the prevention and treatment of deep vein thrombosis and pulmonary embolism.Curr Opin Anaesthesiol.2006;19(1):52–58.
- Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med.2005;118(9):978–980.
- Konstantinides S, Schafer K, Neels JG, Dellas C, Loskutoff DJ. Inhibition of endogenous leptin protects mice from arterial and venous thrombosis. Arterioscler Thromb Vasc Biol.2004;24(11):2196–2201.
- Coon WW. Risk factors in pulmonary embolism. Surg Gynecol Obstet.1976;143:385–390.
- Koenig SM. Pulmonary complications of obesity. Am J Med Sci.2001;321(4):249–279.
- Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost.2003;89(3):493–498.
- Frezza EE, Chiriva-Internati M. Venous thromboembolism in morbid obesity and trauma. A review of literature. Minerva Chir.2005;60(5):391–399.
- Pulipati RC, Lazzaro RS, Macura J, Savel RH. Successful thrombolysis of submassive pulmonary embolism after bariatric surgery: expanding indication and addressing the controversies. Obes Surg.2003;13(5):792–796.
- Sugerman HJ, Sugerman EL, DeMaria EJ, Kellum JM, Kennedy C, Mowery Y, Wolfe LG. Bariatric surgery for severely obese adolescents. J Gastrointest Surg.2003;7(1):102–107.
- Dahl OE, Carpini JA, Colwell CS, Froswtick SP, Haas S, Hull RD, Laporte S, Stein PD. Fatal vascular outcomes following major orthopedic surgery. Thromb Hemost.2005;93(5):860–866.
- Kasper EK, Hrubn RH, Baughman KL. Cardiomyopathy of obesity a clinical pathologic evaluation of 43 obese patients with heart failure. Am J Cardiol.1992;70(9):921–924.
- Alpert MA. Obesity: cardiomyopathy pathophysiology and evolution of the clinical syndrome. Am J Med Sci.2001;321(4):225–236.
- Wang MY, Unger RH. Role of PP2C in cardiac lipid accumulation in obese rodents and its prevention by troglitazone. Am J Physiol Endocrinol Metab.2005;288(1):e216–e221.
- McGavock JM, Victor RG, Unger RH, Szczepaniak LS; American College of Physicians and the American Physiological Society. Adiposity of the heart, revisited. Ann Intern Med.2006;144(7): 517–524.
- Brenn BR. Anesthesia for pediatric obesity. Anesthesiol Clin North Am.2005;23(4):745–764.
- Inselman LS, Milanese A, Deurloo A. Effect of obesity on pulmonary function in children. Pediatr Pulmonol.1993;16(2):130–137.
- Spector A, Scheid S, Hassink S, Deutsch ES, Reilly JS, Cook SP. Adenotonsillectomy in the morbidly obese child. Int J Pediatr Otorhinolaryngol.2003;67(4):359–364.
- Tseng CH, Chen C, Wong CH, Wong SY, Wong KM. Anesthesia for pediatric patients with Prader-Willi syndrome: report of two cases.Chang Gung Med J.2003;26(6):453–457.
- Cely CM, Arora P, Quartin AA, Kett DH, Schein RMH. Relationship of baseline glucose homeostasis to hyperglycemia during medical critical illness. Chest.2004;126(3):879–887.
- Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med.2001;345:1359–1367.
- El-Solh A, Sikka P, Bozkanat E, Jaafar W, Davies J. Morbid obesity in the medical ICU. Chest.2001;120:1989–1997.