Artículo de Revisión

Perioperative Management of The Diabetic Child

Ana Sofía Del Castillo*, Troy Holder**, Norma Sardi***

* Médico Anestesiólogo, Hospital Santo Tomás. Funcionario del Hospital del Niño, Ciudad de Panamá, Panamá, anasofia113@gmail.com.
** Médico Anestesiólogo, Hospital Santo Tomás. Funcionario del Hospital del Niño, Ciudad de Panamá, Panamá.
*** Médico. Funcionario en Patología Clínica, Hospital Santo Tomás. Profesor titular de Patología Humana en la Universidad Latina de Panamá, Ciudad de Panamá, Panamá.

Recibido: noviembre 27 de 2009. Enviado para modificaciones: enero 28 de 2010. Aceptado: octubre 13 de 2010.

Pediatric patients with diabetes mellitus are managed during the perioperative period by pediatric anesthesiologist who carefully monitors glycemia levels, in addition to the type of surgery and the pathophysiology of the disease. This article represents a practical guide, an algorithm for managing pediatric diabetic patients undergoing surgery, whether under general or regional anesthesia.

Diabetes mellitus is a metabolic condition that has been known for centuries. The first descriptions of its clinical characteristics date back to 1550 BC. Notwithstanding that most young diabetic patients currently enjoy happy and productive lives, just 80 years ago children and adults suffering from this condition had a limited life expectancy and usually died within the first two years after being diagnosed (1).

Generally speaking, diabetes mellitus can be defined as a clinical syndrome resulting from the inadequate utilization of glucose and metabolic dysfunction. It can be secondary to an insulin secretion disorder or to a reduction in its biological effectiveness (2).

The incidence of diabetes mellitus -both type 1 and type 2- in children has increased in the last few years (3) and has become a real challenge for the anesthesiologist due to its complex management that requires considering the pathophysiology of the disease, in addition to the specific treatment regime of the child, glycemic control, the type of surgery, for how long has the condition been present, and expectations in terms of postoperative control.

In view of the above, and considering the diversity and complexity of the current treatment for diabetes, the perioperative plan for the diabetic child must always be prepared in consultation with the pediatric endocrinologist.

The purpose of this article is to provide practical schemes for the perioperative management of the diabetic child: a subgroup of patients within the pediatric population with especial needs.

The methodology used in preparing this article was a systematic review of the available literature on the perioperative management of the diabetic child using the following databases: Pubmed, MEDLINE, Ovid, Cochrane. However, these databases are limited and the few literature reviews available on the topic are over ive years old (4-9).

The advent of new insulin analogues, new insulin continuous administration systems, and the growth in the number of children with type-2 diabetes because of increased pediatric obesity, makes the perioperative management of blood sugar levels in the pediatric patient a more demanding challenge for the anesthesiologist.

CLASSIFICATION AND ETIOLOGY OF DIABETES MELLITUS

Diabetes mellitus is usually divided into two large groups (10-12):

• Type 1 - caused by the destruction of the pancreatic Beta (β) cells, usually related to the immune response associated with human leukocyte antigens Class 2.

Viruses such as Coxsackie B and some toxins have been suggested as potential causal agents in some patients. This combined pathophysiology results in an absolute insulin deficiency.

• Type 2 - The etiology of type-2 diabetes is a mixture of insulin resistance of the peripheral tissues and a relative insulin deficiency. Initially this type of diabetes was mainly an adult condition; however, due to the increasing numbers of obese children, there is a growing number of children diagnosed with type-2 diabetes.

There are other less common types of diabetes that are summarized in Table 1 (8):

The global incidence of Type-1 diabetes is highly variable (13) but apparently it tends to increase in the various populations around the world (14). The increasing number of obese North American children has contributed to the progressive increase in the incidence and the prevalence of type-2 diabetes in this population group (15).

Consequently, this information may be extrapolated to the Latin American reality. According to the results of the "National Health and Nutrition Examination Survey III" (19881994), approximately 100,000 North American teenagers - 12 to 19 years old - had diabetes and out of this number, 31% had type-2 diabetes (16).

OPTIONS FOR MANAGING DIABETES MELLITUS IN CHILDREN

Type-1 diabetes will always require insulin treatment. There are increasing numbers of insulin preparations available in the market (please refer to Table 2). Glargine (glargine insulin; Sanofi-Aventis, Bridgewater, NJ) (17), a new insulin product, is a long-acting preparation that delivers a relatively constant level of circulating insulin avoiding pronounced peaks (18). Another therapeutic option is the insulin pump; a device that administers a continuous subcutaneous insulin infusion (typically a fast-acting insulin) at a constant basal rate that is supplemented with additional insulin boluses before meals and snacks to control hyperglycemia. In carefully selected patients this modality has proven to be superior to the administration of injections (19,20).

Moreover, in Type-2 diabetes, most pediatric patients are managed with insulin and / or metformine (21). Metformine is an FDA approved drug for pediatric use (22). Its mechanism of action reduces the production of glucose by the liver and increases insulin sensitivity in the peripheral tissues (23,24). In older teenagers other drugs such as sulphonylureas (25) may be used; sulphonylureas promote insulin secretion, while thiazolidinediones (26,27) increase insulin sensitivity in the muscle and fatty tissue.

With regards to the new group of drugs for managing type-2 diabetes whose MOA inhibits dipeptidyl peptidase (DDP-4) and increases the level of active incretin hormones (28), its use is not recommended in patients under 18 years of age because there are no studies about its safety and efficacy in children (29). Sitagliptine is the molecule currently available in Latin America.

METABOLIC RESPONSE TO SURGERY AND ANESTHESIA

Insulin is the most important anabolic hormone. Its role is to promote the reuptake of glucose by the muscle and adipose tissue, as well as to suppress the metabolic pathways that promote the production of glucose by the liver (glucogenolysis y glucogenesis). The anti-insulin hormones have the opposite effect; i.e. to raise blood sugar levels by stimulating glucogenolysis and glucogenesis, increase li-polysis and ketogenesis. The group of counterregulatory hormones includes epinephrine, glucagon, cortisol and growth hormone (31).

Trauma and surgical stimuli trigger a complex neuroendocrine response to stress, including the suppression of insulin production and increasing the anti-insulin hormones, particularly cortisol and catecholamines (32). The end result is a catabolic status with increased glucose production by the liver and rupture of the protein and fat molecules (33). All of these changes in the diabetic patient result in marked hyperglycemia and a probable diabetic ketoacidosis (34).

ADVERSE CONSEQUENCES OF HYPERGLYCEMIA

Although clinical studies have not shown a consistent relationship between perioperative blood sugar control and the short term risk of infection and morbidity (35), many endorse the accepted recommendation about maintaining close to normal glycemia as part of the standard care for managing the diabetic patient (36-38).

Hyperglycemia affects wound healing by altering collagen production that lowers the tensile strength of surgical wounds (39). Additionally, hyperglycemia has adverse effects on neutro-phil function, chemotactic, phagocytic, and bactericidal activities (40).

There is no evidence to support the use of any particular inhaled anesthetic agent, since all of them compromise insulin release. Induction must be done taking into account the delayed gastric emptying and the autonomic neuropathy present in these children that give rise to a reduced response to atropin and ephedrin, resulting in extreme hypotension, bradycardia or tachycardia (41).

Regional, epidural or spinal anesthesia reduces the normal hyperglycemic response because the sympathetic block affects the production of counterregulatory hormones. However, the administration of large doses of local anesthetics has been associated to mio-cardial depression; peripheral neuropathy must always be ruled out when selecting a regional technique (42).

PERIOPERATIVE EVALUATION

It is important to remember that diabetic children rarely exhibit any vascular, neurological or renal complications that are usually present in adult diabetics; thus the management of pediatric patients shall strive to control glucose homeostasis (43).

The management of pediatric patients can be summarized as follows:

1. Identifying any related or coexisting pathologies.

2. Correcting any acid-base, hydroelectrolytic or volemic disorders prior to surgery.

3. Achieving a satisfactory blood glucose control.

4. Preventing hypoglycemia.

5. Insulin administration to inhibit any cata-bolic condition (proteolysis, lipolysis and ketogenesis), if necessary (44).

When surgery is an elective procedure, it should be deferred until adequate metabolic control is achieved. Practically speaking, this means (8):

• No ketonuria.

• Normal serum electrolytes

• Close to normal glycated hemoglobin (HbAlc):

- Less than 5 years old, 7 to 9 %

- 5 to 13 years old, 6 to 8.5 %

- Over 13 years of age, 6 to 8 %

There should be a pre-operative consultation at least 10 days before the surgical procedure to ensure an adequate metabolic control, in close relationship with anesthesiology and endocrinology. Furthermore, these patients must be scheduled for surgery early in the day to avoid extended fasting and to facilitate the adjustment of the diabetic treatment scheme.

In case of an emergency surgical intervention (trauma or acute surgical pathology), the patient should be managed jointly with endocrinology and anesthesiology. However, despite poor metabolic control, surgery cannot be avoided in an emergency but the patient must be subject to clinical and biochemical analyses and any metabolic imbalance must be corrected, unless the indication for surgery calls for immediate intervention.

These patients are usually dehydrated so the mainstay of treatment is rehydration and a continuous insulin intravenous infusion.

PREOPERATIVE MANAGEMENT

The management of the pediatric patient before, during and after surgery or diagnosis is aimed at maintaining a normal glucose level; i.e. plasma sugar between 100 y 200 mg/dL. The goal is to keep the patient within this range to reduce the risk of osmotic diuresis, dehydration, hydroelectrolytic imbalance, metabolic acidosis, infection and hypoglycemia.

The diabetic child scheduled for minor surgical interventions can be admitted on the same day of surgery, while those scheduled for major surgical procedures should be admitted one day before surgery.

In the morning of the surgical procedure, short or fast-acting insulin should be avoided, unless the blood sugar level exceeds 250 mg/dL. If this were the case, a fast or short-acting insulin dose should be administered using a "correction factor" which is the expected drop in blood sugar after the administration of 1 U of insulin. The correction factor is calculated using the "1,500 rule". This rule consists of dividing 1,500 into the usual total dose of insulin used by the child. For example, if the child typically uses 50U of insulin, the correction factor will be 1,500 ÷ 50 = 30; this means that 1 U of insulin in this patient should reduce the plasma glucose concentration by 30mg/dL. Although there are other correction factors for regular insulin and for lispro insulin (45), the "1,500" correction factor is a safe and practical approach to correct hyperglycemia during the pre-operative period in patients who are receiving subcutaneous fast-acting or regular insulin, and in patients that will be managed with an insulin infusion during surgery.

Type-2 diabetic patients not previously treated with insulin shall get a fast-acting subcutaneous insulin dose of 0.1 U/kg when blood glucose levels are above 250 mg/dL. However, each child should be treated on a case-by-case basis, in accordance with his/her baseline treatment.

For practical purposes, the trans-operative management should be divided into four large groups:

• Children taking oral glucose-lowering agents

• Minor outpatient procedures

• Minor and intermediate inpatient procedures

• Major procedures

Children taking oral glucose-lowering agents

• If the child takes metformin, the agent must be discontinued 24 before the procedure to prevent the risk of lactic acidosis, dehydration, hypoxemia and poor tissue perfusion (46,47).

• If the child is taking other drugs such as sulfonylureas and thiazolidinediones, these should be discontinued on the morning of the surgical procedure.

MINOR OUTPATIENT PROCEDURES

In these cases there is no need to stop the administration of insulin whether subcutaneous or intravenous insulin bolus. However, although some studies recommend insulin infusions, even for minor pediatric outpatient procedures (4), we must realize that these procedures were done before the fast-acting insulin -with effects similar to the intravenous administration after subcutaneous injection-became available.

Notwithstanding the lack of studies on the use of fast-acting insulin in children, there is proven evidence in type-2 adult diabetics showing the comparable effectiveness of the fast-acting agent versus the continuous infusion (48).

MINOR AND INTERMEDIATE INPATIENT PROCEDURES

Management of these types of patients depends on the child's baseline treatment regime::

• Combination of fast and slow-acting insulin:

- On the day of surgery, these patients should be administered 50 % of the usual intermediate or slow-acting morning insulin dose.

• Use of glargine insulin

- If the child uses glargine insulin in the afternoon, this insulin should not be administered on the morning of the surgical procedure.

- If the child uses glargine insulin in the morning, the complete dose must be administered on the morning of surgery to prevent ketosis.

• Use of subcutaneous insulin pumps

- For surgeries less than 2 hours long, the pump may be used at the basal rate for that time of the day.

- For surgical procedures exceeding 2 hours or when the anesthesiologists is not familiar with these systems, a transition to an intravenous insulin infusion is recommended.

MAJOR PROCEDURES

We must remember that the stimulation of the sympathetic nervous system may have a direct impact on glucose homeostasis. The circulating epinephrine stimulates the Alfa (α) 2-receptors, reducing the pancreatic insulin release and increasing glucogenesis. For this reason, adequate analgesia during surgery is of the essence in this group of patients, so as to minimize sympathetic stimulation (49).

Major procedures are those procedures expected to last over two hours or with bleeding potential. Under these circumstances, there studies in children (7) as well as in adults (49) show the superiority of insulin infusions over subcutaneous injections for an optimum blood sugar control.

The suggested management is as follows:

• Patients should receive their usual insulin dose the day before the procedure .

• In the morning of surgery, an intravenous 10 % dextrose infusion in normal saline solution should be started as a maintenance dose, together with an intravenous insulin infusion that is administered simultaneously to maintain the blood sugar levels within the 100-200 mg/dL range.

- The maintenance of intravenous fluids depends on the size of the child and may be estimated on a body-weight basis (4 mL/Kg for the first 10 kg, 2 mL/kg from 11-20 kg, and 1 mL/kg per each kilogram above 20 kg) and according to body surface area (1.5L/m²/d).

• Since pre-pubertal children are more sensitive to insulin (50), the dose to be administered depends on the age of the patient:

- For pre-pubertal children (under 12 years of age), insulin requirements are typically 0.6 to 0.8 U/kg/day.

- Teenagers require a dose of 1.0 a 1.5 U/kg/day.

- Because type-2 diabetic patients are insulin-resistant, their requirements will be higher. In children under 12 years of age, the dose used is 1 U of insulin per 5 g of dextrose; children over 12 years old use 1 U of insulin per 3 g of dextrose.

POST-OPERATIVE MANAGEMENT

Blood sugar levels should be strictly monitored, together with the presence of ketonu-ria, the renal function and electrolyte levels.

Do not forget that surgical trauma, inactivity, pain, nausea, vomiting and poor food intake by mouth have a significant impact on glucose homeostasis.

As soon as the patient is able to take food by mouth, the usual treatment regime should be re-established, including insulin and oral glucose-lowering agents. The infusion of fluids should be discontinued.

Those patients unable to take food by mouth shall continue to receive dextrose and electrolytes solutions, maintaining blood sugar levels between 100 to 200 mg/dL, either with intravenous or subcutaneous insulin boluses.

The pediatric diabetic patient must be managed with a holistic approach, including Anesthesiology and Endocrinology care and taking into account his/her baseline treatment regimen, in addition to age, weight, puberty and surgical procedure. Based on these factors, the anesthesiologist has to establish a work-program for the perioperative management of these patients, in accordance with the inherent complexity of diabetes.

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