What concentration of dextrose should be given to an unconscious patient?

Acute complications

Diabetes can lead to coma. Hypoglycaemic coma is the main acute complication of diabetes, is growing in frequency with the trend towards tighter metabolic control of diabetes, and is usually the result of one or more of the above factors. Less common causes are shown in Table 6.8. Many insulin-treated patients are liable to hypoglycaemia, due to an imbalance between food intake and usage, and insulin therapy. Hypoglycaemia can be of rapid onset and may resemble fainting. Adrenaline (epinephrine) is released, leading to a strong and bounding pulse, sweaty skin, and often anxiety, irritability and disorientation, before consciousness is lost. Occasionally, the patient may convulse.

The patient should be treated immediately (Table 6.9); hypoglycaemia must be quickly corrected with glucose or brain damage can result. Glucose will cause little harm in hyperglycaemic coma but will improve hypoglycaemia. Never give insulin since this can cause severe brain damage or kill a hypoglycaemic patient. Assess the glucose level with a testing strip.

If the patient is conscious, give glucose solution or gel (GlucoGel) immediately by mouth or 10 g sugar but, if the patient is comatose, give 10–20 mL of 20–50% sterile dextrose intravenously or, if a vein cannot readily be found, glucagon 1 mg intramuscularly. On arousal, the patient should also be given glucose orally, usually in the form of longer-acting carbohydrate (e.g. bread, biscuits).

Other diabetics are difficult to control (brittle diabetes – a term usually used in association with adolescent girls who may be self-harming) and more prone to ketosis, severe acidosis and hyperglycaemia (diabetic coma), the result of a relative or absolute deficiency of insulin. In patients under treatment, it may be precipitated by factors such as infections.

Hyperglycaemic coma usually has a slow onset over many hours, with deepening drowsiness (but unconsciousness is rare, so an unconscious diabetic should always be assumed to be hypoglycaemic), signs of dehydration (dry skin, weak pulse, hypotension), acidosis (deep breathing), and ketosis (acetone smell on breath and vomiting) mainly in type 1 diabetes. If it is certain that collapse is due to hyperglycaemic ketoacidotic coma, the immediate priority is to establish an intravenous infusion line. This enables rapid rehydration to correct dehydration and electrolyte (especially potassium) losses, and the administration of insulin. Blood should be taken for baseline measurements of glucose, electrolytes, pH and blood gases. Raised plasma ketone body levels can be demonstrated with a testing strip such as Ketostix (Ames). Insulin is then started, such as 20 units i.m. stat. Medical help should be obtained as soon as possible.

Coma in a diabetic patient, though usually due to hypo- or hyperglycaemia, may have other causes such as myocardial infarction (Ch. 5).

Inborn Errors of Metabolism (Enzyme Deficiencies)

Hypoglycemia that develops in infancy and persists into adult life with effective therapy can be caused by enzymatic defects in carbohydrate, protein, or fat metabolism245 (seeTable 38.10). Hypoglycemia usually becomes apparent later in infancy as the intervals between feedings become longer.

Abnormalities in the metabolism of carbohydrates are usually due to enzymatic deficiencies in the synthesis or metabolism of glycogen, gluconeogenesis, or metabolism of galactose or fructose. Glycogen storage diseases (GSDs) are due to different enzyme deficiencies that present early in childhood and are usually characterized by hypoglycemia after short fasting periods, that may have mild to moderate ketosis, and may present with or without hepatomegaly and have no response to glucagon stimulation. GSD type 0 is caused by glycogen synthase deficiency, which results from mutations inGYS2 and does not cause hepatomegaly, but is characterized by preprandial ketotic hypoglycemia and postprandial hyperglycemia and lactic acidemia. GSD type Ia (von Gierke disease) is caused by mutations inG6PC, the gene that encodes glucose-6-phosphatase hydrolase activity. It occurs in approximately 1 of every 100,000 live births272 and accounts for 80% of GSD type I cases. Given that glucose-6-phosphatase is the final enzyme in the hepatic release of glucose from gluconeogenic and glycogenolytic pathways, absence of its activity results in low rates of endogenous glucose production and severe fasting hypoglycemia272 with no glycemic response to administered glucagon. Clinical findings include failure to thrive, hepatomegaly (due to both glycogen and fat accumulation), hypertriglyceridemia, accelerated lipolysis and ketogenesis, hyperuricemia, platelet dysfunction, andmarked lactic acidosis (from the metabolism of glucose-6-phosphate). With the exception of hepatomegaly, these abnormalities can be reversed by effective prevention of hypoglycemia with frequent feedings during waking hours and continuous intragastric glucose infusion during sleep or bedtime administration of large doses of uncooked cornstarch. Liver transplantation corrects hypoglycemia and the associated metabolic abnormalities. Late complications include progressive renal disease due to glycogen accumulation in the kidneys and hepatic adenomas. GSD type Ib is caused by mutations inG6PT1, the glucose-6-phosphate microsomal transporter. Their clinical presentation and biochemical findings are identical to GSD type Ia, but these patients also have chronic or intermittent neutropenia and neutrophil dysfunction, and are susceptible to recurrent infections. The diagnosis of GSD type Ia and type Ib is confirmed by mutation analysis ofG6PC andG6PT1. Hypoglycemia is less prominent in GSD type III (hepatic amylo-1,6-glucosidase deficiency due to mutations inAGL), GSD type VI (hepatic glycogen phosphorylase deficiency due to mutations inPYGL), and GSD type IX (hepatic phosphorylase kinase deficiency due to mutations inPHKA2) because hepatic gluconeogenesis is preserved and these defects in glycogenolysis are rarely complete. These forms of GSD are rare and are treated with avoidance of hypoglycemia by frequent administration of frequent high-carbohydrate feedings and uncooked cornstarch, particularly at bedtime; in GSD type III, a high-protein diet can be of benefit.

Coma in Diabetes

Three types of coma occur in diabetes:

Hypoglycemic coma.

Hyperglycemic coma, either ketoacidotic coma (diabetic ketoacidosis: DKA), or hyperosmolar, nonketotic coma.

Hypoglycemia

Hypoglycemia is the most frequent complication in patients with diabetes taking oral hypoglycemic drugs [43–45].

Presentation: In general, hypoglycemia caused by oral hypoglycemic drugs is more dangerous and of longer duration than hypoglycemia caused by insulin [46], and the most dangerous hypoglycemic attacks are those that result from long-acting drugs, such as chlorpropamide, and later sulfonylureas, such as glibenclamide [40]. Sulfonylureas are mostly used by elderly people, and the characteristic warning symptoms of hypoglycemia (dizziness, breathlessness, sweating, and a feeling of hunger) are often absent or not well-interpreted.

Neurological symptoms are common and hypoglycemia can cause hemiplegia, which can be confused with neurological symptoms of other origin (transient ischemic attack, stroke, etc.). A bilateral case has been reported [47].

A 68-year-old man started to take glibenclamide and 1 week later developed a blurred voice and a hemiplegia, with a blood glucose of 1.4 mmol/l. Ten minutes after intravenous glucose 50 g his motor function returned to normal. Six hours later he developed slurred speech and left-sided hemiplegia; his blood glucose was 1.9 mmol/l. During glucose administration his deficit resolved.

A 75-year-old man taking gliclazide 80 mg bd and metformin 850 mg tds became hypoglycemic and was treated successfully [48]. All hypoglycemic drugs were withdrawn, but he received more through his doctor’s prescription computer and again became hypoglycemic on two occasions. On the second he became unconscious for 4.5 hours and his plasma glucose was 1.2 mmol/l. After resuscitation his abbreviated mental test was 5/10 and did not improve. He later became very aggressive and died of bronchopneumonia.

Three patients became comatose because of hypoglycemia; all had general malaise, reduced food intake, and vomiting; glucose had to be given for a long time and one patient died with pneumonia [49].

Frequent attacks of hypoglycemia can result in encephalopathy, and after withdrawal of the hypoglycemic drug cerebral injury can persist. It is not exceptional for prolonged hypoglycemic coma to end fatally [50,51]. In 494 cases of severe hypoglycemia, 10% of the patients died and 9% had permanent sequelae [52].

Hypoglycemia has been reported in a worker, not wearing a mask, working with a machine preparing ultrafine sulfonylurea powder [53].

In a retrospective study 400 doctors in Germany were asked to compare the characteristics of severe hypoglycemia in patients in acute care induced by glimepiride and glibenclamide [54]. Only 24 responded (6%). There were no differences in clinical characteristics or time course.

Treatment

Patients with undiagnosed or undertreated GSD type I are at increased risk of death, usually from hypoglycemic comas, seizures, metabolic acidosis, or, in those with GSD type Ib, sepsis from neutropenia.49 Rarely, hepatocellular carcinoma is a cause of death. Management centers on preventing the acute metabolic derangements and potential long-term complications and enabling the patient to attain normal psychological development and a good quality of life.59,61

Consensus guidelines for the management of GSD type I have been proposed.59,61 Biomedical targets for good metabolic control include a preprandial blood glucose level higher than 63 to 77 mg/dL (3.5 to 4.3 mmol/L), urine lactate-to-creatinine ratio higher than 0.06, high-normal serum uric acid level, venous blood base excess higher than −5 mmol/L, bicarbonate level higher than 20 mmol/L, serum triglyceride level lower than 6 mmol/L, and body mass index (BMI) between 0 and 2 standard deviations from normal. In addition, for GSD type Ib, demonstrating a normal fecal α1-AT level is desirable (see Chapter 28).59,62 Because optimal glycemic control is not always possible and the risk of severe hypoglycemia is high if delivery of glucose is interrupted inadvertently, serum lactate levels should be kept at the high end of normal because lactate is an alternative fuel for the brain.

Nutritional supplementation has become the mainstay of therapy for GSD type I. Frequent, high-carbohydrate, daytime feedings, such as uncooked cornstarch, or continuous nighttime drip feedings, or both, allow the steady release of glucose and lead to improved metabolic control and normalized growth and development.52,62 A biochemical target is to maintain the serum glucose level above 70 mg/dL (3.9 mmol/L). Uncooked cornstarch in a dose of 2 g/kg every six hours (6 to 8 mg of glucose/kg/minute) has been suggested; however, alternative regimens have been implemented successfully.

For infants, when the diagnosis of GSD type 1 is confirmed, a formula that does not contain fructose or galactose should be prescribed. Frequent daytime feedings and continuous nocturnal administration are required, with the rate of delivery needed to maintain euglycemia being ≈8 mg/kg/minute. Morning feedings should be given quickly after discontinuation of the nighttime drip to avoid hypoglycemia. As solids are introduced, high-carbohydrate foods should be emphasized. These patients require special attention during acute illnesses that may affect oral intake or metabolism because they can become hypoglycemic quickly.

Prophylaxis with antibiotics (e.g., trimethoprim-sulfamethoxazole) is recommended for patients with GSD type 1b and severe neutropenia or recurrent bacterial infections.61 Granulocyte colony stimulating factor (GCSF) has been used with success in patients with GSD type 1b to improve hematologic parameters and neutrophil function and reduce the morbidity associated with severe bacterial infections.63 Splenomegaly may worsen with GCSF therapy, and bone marrow aspiration before and during GCSF therapy may be prudent, given rare occurrences of acute myelogenous leukemia (AML) in patients with GSD type 1b.61 Both GCSF and inflammatory bowel disease raise the risk of osteopenia, and monitoring of bone density is advised.

Adenoviral-mediated gene replacement therapy of recombinant Glu-6-Pase in a canine model of GSD type Ia deficiency, which has all of the major features of GSD type 1a in humans, has led to encouraging results and may be an option in humans in the future.64 An alternative approach, human hepatocyte transplantation, has been performed in a single patient with GSD type 1a with near-resolution of hypoglycemic episodes; however, hypoglycemia subsequently recurred, likely because of the lack of ongoing immunosuppression to reduce the likelihood of recipient rejection of transplanted donor hepatocytes.65 Hepatocyte transplantation, with the use of standard post-transplantation immunosuppression, has been performed successfully in an 18-year-old male adolescent with GSD type 1b, with euglycemia maintained up to 2 years post-transplantation.66

Liver transplantation has corrected the metabolic error in patients with GSD type I and permitted catch-up growth, even in patients in the third decade of life.67,68 Neutrophil counts and function, however, are only variably improved after liver transplantation in patients with GSD type 1b.67

Effect of Blood Glucose

In adult humans, hypoglycemia of mild or moderate degree is not associated with a change in CBF.42,43 During hypoglycemic coma, however, CBF increases.44 In experimental animals, CBF increases during hypoglycemic coma and correlates with a loss of electrical activity on the electroencephalogram.45-48 The increase in CBF appears to result from increased systemic blood pressure and loss of autoregulation.49 Thus, if the blood pressure is reduced during hypoglycemic coma, CBF returns to baseline.

Pryds and colleagues-50 reported increased CBF in preterm infants with hypoglycemia. CBF was significantly higher at 26 mL/100 g/minute in infants with blood glucose levels lower than 30 mg/dL than in those with blood glucose levels greater than 30 mg/dL, in whom CBF was only 11.8 mL/100 g/minute. None of the infants with low blood glucose levels exhibited clinical signs of hypoglycemia, nor did any progess to coma. Moreover, no abnormalities of the electroencephalogram were apparent. These data suggest that the response to hypoglycemia in preterm infants is different from that in adults. Furthermore, cerebral glucose metabolism may be critically important to provide the energy requirements of the preterm brain. These findings are in agreement with those for a study in which Altman and colleagues51 reported that cerebral oxygen metabolism in some preterm infants may be minimal, and that cerebral glucose metabolism may provide the necessary energy for preterm cerebral growth and function.

In summary, the newborn circulation shows many of the same characteristics as those of the adult circulation. The magnitude of the CBF responses and the quantitative relationships of CBF with changes in blood pressure and with a variety of systemic factors have not been fully elucidated. The relationship of these circulatory regulatory responses with the development of IVH and their role in its pathogenesis in sick preterm infants remain to be determined.

Pancreatic and islet transplantation: Scarcity, graft loss, and immunosuppression

Despite continuing advances in insulin delivery technology and recombinant insulins, diabetes and its complications still claim countless lives as a result of ketoacidosis, hypoglycemic coma, or chronic hyperglycemia-induced cardiovascular, eye, nerve, and kidney damage. As an alternative to insulin, biological β cell replacement therapies including pancreas and islet transplantation are established therapies capable of fully restoring glucose control and achieving insulin independence. Evidence also supports that long-term restoration of normoglycemia can prevent or forestall end-organ damage.17–19 Nevertheless, these approaches suffer from critical limitations, most notably the shortage of available organs and the need for lifelong immunosuppression. Utilizing the approximately 31,800 cadaver donors available in the United States annually, pancreatic and islet transplantation, while rapidly effective in restoring insulin independence in > 95% and > 80% of recipients, respectively, are wholly insufficient to meet the burden of diabetes in the United States.20 Islet transplantation is further hampered presently by the general requirement of multiple donor pancreata to achieve insulin independence due to inadequate engrafted islet mass following isolation and intrahepatic portal vein transplantation.21 Consequently, very few diabetic patients can be treated by current β cell replacement methods.

With donor scarcity being a major challenge that prevents treating all but a few patients with diabetes, it is logical to pursue using PSCs as an abundant cell source, which can be expanded many fold ex vivo to generate glucose-responsive IPCs. However, an ideal β cell replacement therapy not only strives toward generating an abundant supply of functional cells but also aims to deliver IPC into a minimally invasive, accessible, and potentially retrievable site that is clinically applicable. An additional goal is to provide a microenvironment that supports engraftment of a high islet mass which can be sustained and protected from innate, allo-, and autoimmune destructive processes. Achieving these last two goals will permit more widespread delivery of a safe and durable therapy.

The success of clinical islet transplantation, achieved by intraportal delivery of cadaver islets, provides proof-of-concept for transplanting IPCs into the liver to effectively restore normoglycemia and reverse diabetes. However, in the long run, transplanting IPCs intraportally is not considered ideal for several reasons. First, allogeneic, unmanipulated IPCs would still likely require immunosuppression to prevent rejection if delivered into this site, as the intraportal route precludes macro- or microencapsulation for immunoprotection. Second, instant blood-mediated inflammatory reaction (IBMIR) can incite inflammation and results in poor engraftment. Furthermore, cells are exposed to high levels of toxic orally administered immunosuppressive medications in the portal circulation, particularly tacrolimus. Lastly, without containment of the cells by some physical or molecular means, if teratoma(s) developed it would be very difficult to treat in this location. While there are disadvantages in the long run and the liver would certainly not be a site of an ideal therapy, there are already well-established successful techniques for minimally invasive intraportal transplantation of cadaver islets which could be easily adapted to IPCs. In addition, while not ideal, currently available immunosuppression is highly successful in preventing rejection in the long-term in many patients without significant side effects. Thus, the intraportal route combined with the use of immunosuppressive medications and anti-inflammatory medications that are standard of care in clinical islet transplantation could logically provide a viable site for the transplantation of IPCs, at least for early proof-of-principle preclinical nonhuman primate studies or early phase pilot clinical trials. It is also hoped that developing technologies in genome editing, matrix biology, immunosuppression, and anti-inflammatory medications could ultimately be marshaled to mitigate the negative aspects of intraportal delivery.

How much dextrose does an unconscious patient need?

What is 10% dextrose used for?

Which IV fluid should be given to an unconscious hypoglycemic patient?

Can you give 20% dextrose peripherally?