A practical approach to hyperglycemia management in the intensive care unit: evaluation of an intensive insulin infusion protocol

STUDY OBJECTIVES: To evaluate the effectiveness and safety of maintaining a target blood glucose concentration of 91-130 mg/dl with a standardized, nurse-managed, intensive insulin infusion protocol outside a study setting, and to determine if a statistically significant favorable effect on morbidity and mortality was achieved. DESIGN: Retrospective, observational, chart review. SETTING: Medical and surgical intensive care units (ICUs) in a community teaching hospital. PATIENTS: One hundred forty-three adult patients who received insulin infusions managed at the discretion of the physician over a 1-year period before initiation of the protocol (control group), and 70 patients who received insulin infusions over a 6-month period with infusion dosages titrated by using the protocol (protocol group). MEASUREMENTS AND MAIN RESULTS: Episodes of hypoglycemia, time within target range, mean blood glucose concentration, frequency of measurement, length of ICU stay, duration of mechanical ventilation, and overall mortality were collected. Hypoglycemic episodes were not significantly different between the groups. Blood glucose concentrations were within target range in 34% of all measurements in the protocol group compared with 23% in the control group (p<0.001, relative risk [RR] 1.48, 95% confidence interval [CI] 1.38-1.58). Once target range was reached on one measurement, 43% of concentrations remained in target range in the protocol group compared with 29% in the control group (p<0.001, RR 1.47, 95% CI 1.38-1.56). Frequency of measurements was higher in the protocol group versus control group (p=0.01); however, clinical difference was minimal. Protocol group had lower overall mortality rate (27% [19/70] vs 32% [46/143], p=0.45), reduced mean ICU length of stay (16.7 +/- 10.6 vs 18.4 +/- 16.0 days, p=0.37), and less mechanical ventilation time (16.5 +/- 9.7 vs 17.0 +/- 15.0 days, p=0.79). CONCLUSION: The nurse-managed insulin infusion protocol improved glycemic control with minimal hypoglycemic episodes compared with baseline practice. A trend toward decreased mortality, ICU length of stay, sand days of mechanical ventilation was observed. When compared with other published protocols, our insulin protocol displays comparable effectiveness with the use of less-frequent blood glucose measurements.     

Comparison of the Efficacy and Safety of Two Different Insulin Infusion Protocols in the Medical Intensive Care Unit

Background:

New guidelines recommend using less intensive glycemic goals in critically ill patients receiving insulin infusions.

Objective:

To compare the efficacy and safety of a modified insulin infusion protocol (MIIP) with less stringent blood glucose (BG) goals to an intensive insulin infusion protocol (IIIP) in patients in a medical intensive care unit (MICU)

Methods:

Retrospective review of patients receiving an insulin infusion for at least 24 hours. Patients treated for hyperglycemic emergencies were excluded. The primary endpoint of the study was mean area under the BG curve (BG-AUC) at 24 and 48 hours. Other endpoints included mean BG, hours until BG at goal, rate of BG above goal, frequency of BG measurements, and rate of hypoglycemia.

Results:

BG-AUC at 24 hours was similar between the groups (MIIP = 5177.7 ± 1221.3 mg/dL x h vs IIIP = 4850.3 ± 1301.7 mg/dL x h; P = .20). The mean BG level at 24 hours was 225.1 ± 91.1 mg/dL in the MIIP group and 205.7 ± 89.7 mg/dL in the IIIP group (P = .06). In the MIIP group, 61.7% of the BG levels were above goal as compared to 87.5% in the IIIP group (P < .0001). Patients were able to achieve BG goals faster with the MIIP (12.58 ± 10.5 hours vs 29.37 ± 16.8 hours; P < .001). The rate of severe hypoglycemia was lower at 24 hours in the patients following the MIIP (0% vs 0.3%; P = .01).

Conclusion:

The study showed that by having less intensive glycemic goals, goal BG levels can achieved faster and the rate of severe hypoglycemia can decrease.     

Clinical potential of insulin therapy in critically ill patients

Stress of critical illness is often accompanied by hyperglycaemia, whether or not the patient has a history of diabetes mellitus. This has been considered to be part of the adaptive metabolic response to stress. The level of hyperglycaemia in patients with acute myocardial infarction (MI) or stroke upon admission to the hospital has been related to the risk of adverse outcome. However, until recently, there was no evidence of a causal relationship and thus stress-induced hyperglycaemia was only treated with exogenous insulin when it exceeded 12 mmol/L (220 mg/dL). In patients with known diabetes, even higher levels were often tolerated. Recently, new data became available in support of another approach. In this review, we focus on the new evidence and the clinical aspects of managing hyperglycaemia with insulin in critically ill patients, drawing a parallel with diabetes management. Particularly, the 'Diabetes and Insulin-Glucose infusion in Acute Myocardial Infarction (DIGAMI) study' and the 'insulin in intensive care study' have provided novel insights. The DIGAMI study showed that in patients with diabetes, controlling blood glucose levels below 12 mmol/L for 3 months after acute MI improves long-term outcome. In the recent study of predominantly surgical intensive care patients, the majority of whom did not previously have diabetes, it was shown that an even tighter control of blood glucose with exogenous insulin, aiming for normoglycaemia, dramatically improved outcome. Indeed, in this large prospective, randomised, controlled study, 1548 intensive care patients had been randomly allocated to either the conventional approach, with insulin infusion started only when blood glucose levels exceeded 12 mmol/L, or intensive insulin therapy, with insulin infused to maintain blood glucose at a level of 4.5-6.1 mmol/L (80-110 mg/dL). Intensive insulin therapy reduced intensive care mortality by more than 40% and also decreased a number of morbidity factors including acute renal failure, polyneuropathy, ventilator-dependency and septicaemia. Future studies will be needed to further unravel the mechanisms that explain the beneficial effects of this simple and cost-saving intervention. Although available evidence supports implementation of intensive insulin therapy in surgical intensive care, the benefit for other patient populations, such as patients on medical intensive care units or hospitalised patients who do not require intensive care but who do present with stress-induced hyperglycaemia, remains to be investigated.     

The management of diabetic ketoacidosis by continuous infusion of low-dose insulin using the ordinary intravenous plastic bag and tubing

Although the hourly intramuscular insulin regimen has been used in the management of diabetic ketoacidosis (DKA) in Ethiopia for over 7 years, continuous intravenous (IV) insulin infusion has never been previously used. In Tikur Anbessa Hospital, Addis Abeba, in 198788, we used the ordinary IV plastic bag and tubings alone to concurrently infuse the low-dose insulin and hydration solution in the management of 15 episodes of DKA in 13 patients, 5 males and 8 females. Initial blood glucose was over 400 mg/dl and urine ketones 4+ in all, and the level of consciousness ranged from drowsy to coma. Initially, 5 to 10 units of crystalline zinc insulin (CZI) was given IV directly to all but 2 patients. Then CZI was added to the normal saline IV bag and the dose of insulin was adjusted according to fluid requirements while at the same time maintaining the insulin rate at 5 to 10 units/hour until the blood glucose dropped to 250 mg/dl or lower. At this point the IV fluid was changed to 5% dextrose and the insulin infusion was reduced to 2 to 4 units/hour. The mean insulin requirement until the dextrose infusion was initiated was 33.2 +/- 7.3 units, IV fluid requirement was 3.5 +/- 0.8 litres and mean duration of treatment 4.4 +/- 1.6 hours. There was one death which was not due to insulin resistance, while all other patients fully recovered. The study demonstrates that insulin infusion using the ordinary IV plastic bag and tubings is safe, simple, and convenient in the management of DKA and hence should be used whenever indicated and feasible.     

Management of gestational diabetes mellitus and pharmacists' role in patient education.

PURPOSE: The pathophysiology, diagnosis, complications, and management of gestational diabetes mellitus (GDM) are discussed, along with considerations in setting up a pharmacist-run GDM education service. SUMMARY: GDM occurs when there is insufficient insulin secretion to counteract pregnancy-related decreases in insulin sensitivity. GDM can be diagnosed by using the same criteria used to diagnose types 1 and 2 diabetes mellitus (DM): a fasting blood glucose concentration of > 126 mg/dL on two separate occasions or a random blood glucose concentration of > 200 mg/dL on two separate occasions. Complications of GDM include maternal type 2 DM, maternal hypertension, macrosomia, shoulder dystocia, and neonatal hypoglycemia. GDM is managed with medical nutritional therapy (MNT), exercise, and therapy with human or synthetic insulin. The American Diabetes Association recommends starting insulin therapy when MNT fails to maintain plasma glucose concentrations at < or = 105 mg/dL during fasting, < or = 155 mg/dL one hour after eating, or < or = 130 mg/dL two hours after eating. A pharmacist interested in establishing a GDM education service must assess the feasibility of providing such education in his or her practice and whether such a program is needed. Other considerations are developing a curriculum, marketing the service, maintaining records, calculating costs, and obtaining reimbursement. CONCLUSION: GDM can have serious effects if not treated properly. A major part of managing GDM involves educating the patient about diet, exercise, blood glucose self-monitoring, and insulin self-administration. A successful pharmacist-run GDM education service must have a market and prices sufficient to generate profit.     

Comparison of Inpatient Glycemic Control with Insulin Vials Versus Insulin Pens in General Medicine Patients

Background:

The Institute for Safe Medication Practices has recommended against routine use of insulin pen devices for inpatients, but the quality of inpatient glycemic control that is achieved with insulin pens versus insulin vials and syringes has not been compared.

Objective:

To evaluate the quality of glycemic control achieved with insulin vials versus insulin pens in type 2 diabetic general medicine patients.

Methods:

This retrospective cohort study compared glycemic control between 2 groups of patients on rapid-acting insulin protocols: those receiving insulin via patient-specific pen devices and those receiving insulin from patient-specific vials. Patients on a prespecified subacute care floor with a diagnosis of type 2 diabetes and at least 24 hours of glucose monitoring while on an insulin protocol with insulin lispro were included. Glycemic control was compared by area under the curve (AUC) estimations of average overall glucose and average glucose above, below, and within goal range (70-180 mg/dL). Percentages of time above, below, and within goal range were also compared.

Results:

The mean ± SD AUC-estimated average glucose for pens was 160 ± 39 mg/dL compared to 158 ± 45 mg/dL for vials (P = .752). The mean ± SD percentage time within goal range was 68.2% ± 28.1% in the pen group versus 69.4% ± 31.8% percent in the vial group (P = .825). No statistically significant differences were detected between those receiving pens or vials for any outcome before and after adjusting for baseline differences and significant covariates.

Conclusion:

Glycemic control did not differ based on insulin delivery system.     

The somatostatin infusion test for the evaluation of glucose utilization in bezafibrate medication

The utilisation of blood glucose may be used for definition of insulin resistance in type II diabetes mellitus. To evaluate this possibility we adapted an infusion test of somatostatin in 10 normal persons (age 26 +/- 3 years, relative body weight 26 +/- 10% according to Broca) in a randomized cross-over therapy with bezafibrate (3 X 200 mg/die). As the coefficient of variation (VC) of measured blood glucose continuously increased the best time of a steady state was between 90 and 130 min after beginning the infusion (mean VC 8.9%). While insulin remained nearly constant (41 (45; 38) microU/ml) blood glucose dropped by about 14% and reached a steady state of 89 (134; 45) mg/dl. During the therapy of bezafibrate blood glucose was significantly decreased by 36% 130 min after beginning the infusion. Although the effect was not significant during the whole time of the steady state it became evident by a negative correlation with lactate (r = -0.687) and pyruvate (r = -0.843). A correlation with a concomitant decrease of triglyceride and cholesterol also induced by bezafibrate could not be proven. The results show that the infusion test of somatostatin is fitted to measure a steady state of blood glucose and insulin and that it is possible by this technique to quantify a changed utilisation of blood glucose induced by specific therapy.     

Blood cholesterol concentration measured by CR3000: fingerstick versus venous sampling

Currently, the clinical practice of desktop or Point of Care (PoC) analyzers for lipid measurements has gained wide popularity. Designed to quickly perform measurements on microlitre(microL) quantities of blood, these instruments can be used in non-laboratory settings, such as physicians offices or field-testing sites and can provide measurements in whole blood, serum, or plasma, using either venous or capillary blood samples. The aim of this study is to examine the relationship between cholesterol determinations in venous and capillary samples using the CR3000 PoC system. The study was performed on 21 unselected adult volunteers, and no exclusion criteria was adopted. The mean cholesterol concentration for the venous blood samples measured was 164 mg/dL. The values obtained in the capillary blood samples averaged 168 mg/dL, which is only slightly higher (e.g., 2.87%) than the venous sample measurements. Moreover, the total variance was statistically similar for venous and capillary measurements (F value = 1.199, where the upper critical value of the F distribution is 2.124, p < 0.05). The results of our study support the concept that CR3000 total cholesterol testing can be performed safely and accurately in either venous or capillary specimens.     

动态血糖监测系统和胰岛素泵在ICU糖尿病患者的联合应用

目的探讨动态血糖监测系统(CGMS)和胰岛素泵持续皮下注射治疗(CSII)在重症监护病房(ICU)2型糖尿病(T2DM)患者的应用效果。方法将120例T2DM患者随机均分为三组:A组采用CGMS与CSII结合治疗模式(40例),B组采用单纯CSII治疗(40例),C组采用胰岛素多次注射治疗(40例)。后两组采用指端毛细血糖监测法。治疗7d后比较三组血糖控制情况、血糖达标率及血糖漂移情况。结果治疗7d后,A组和B组患者的全日血糖、平均血糖(MBG)、平均血糖波动幅度(MAGF)均较治疗前明显下降,且明显优于C组(P<0.05),低血糖发生次数亦较C组明显减少(P<0.05)。其中,A组MBG、MAGE、低血糖次数均显著低于B组(P<0.05)。结论 CGMS能监测血糖连续的变化曲线,及时发现高血糖和低血糖,与胰岛素泵联合治疗更有利于ICU糖尿病患者血糖的控制,降低低血糖的发生率。     

Glucose metabolism and insulin resistance in sepsis

Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. Even a moderate degree of hyperglycemia appears detrimental for the outcome of critically ill patients, since maintenance of normoglycemia (blood glucose levels 相似文献   

早期综合护理干预对PICU应激性高血糖患儿治疗转归的影响

目的:探讨儿科重症监护室(PICU)应激性高血糖患儿更佳的护理方法.方法:将血糖＞10.1 mmol/L患儿45例随机分为观察组23例和对照组22例.两组患儿均在限糖输注基础上给予胰岛素0.1～0.2 u/kg皮下或静脉注射.观察组采取早期综合护理干预,对照组采取常规护理方法.结果:两组12例患儿中于3天内死亡,其余两组患儿进入危重恢复期时间及血糖恢复正常(＜7 mmol/L)时间有显著性差异(P＜0.05).结论:小剂量胰岛素治疗PICU应激性高血糖安全有效,早期综合护理干预对小剂量胰岛素治疗PICU应激性高血糖治疗转归有重要意义.     

Validation of an insulin infusion nomogram for intensive glucose control in critically ill patients

STUDY OBJECTIVE: To evaluate the effectiveness, safety, and associated patient outcomes of a simplified, nurse-directed insulin nomogram designed to achieve intensive blood glucose level control (target range 90-144 mg/dl). DESIGN: Prospective study with a retrospective control group. SETTING: A medical-surgical intensive care unit (ICU) in a quaternary care, university-affiliated hospital in an urban center. PATIENTS: Eighty-six critically ill adult patients (aged>or=18 yrs) requiring blood glucose control, with 42 in the retrospective control group and 44 in the prospective nomogram group. INTERVENTION: Control patients received insulin subcutaneously or intravenously based on ad hoc insulin sliding scales; nomogram patients received intravenous insulin at a rate specified by the nomogram, based on capillary blood glucose levels measured at the bedside. MEASUREMENTS AND MAIN RESULTS: Insulin infusion in the prospective patient group was titrated by the bedside nurse based on a predefined nomogram to attain the target blood glucose level. The retrospective control group was used as a comparison to assess the safety and effectiveness of the nomogram. Fewer patients in the nomogram (32%) than control (67%) group had a diagnosis of diabetes mellitus on admission. Overall, blood glucose levels in the nomogram group were within the target range 52% of the time versus 20% in the control group (p<0.001). Morning blood glucose levels were significantly lower compared with the control group (mean+/-SD 128+/-32 vs 176+/-50 mg/dl, p<0.001). Nomogram patients achieved target blood glucose levels faster than control patients (median 15 vs 66 hrs, p<0.0001). This improved blood glucose control remained statistically significant after adjusting for baseline differences in diabetes status. Hyperglycemia occurred less often in the nomogram than the control group (14% vs 53%, p<0.0001), and hypoglycemia occurred more often (3.8% vs 2.2%, p=0.004). The frequency of severe hypoglycemia was similar in both groups (0.2% vs 0.4%, p=NS). Such control required slightly more blood glucose checks/day in the nomogram group (7.1+/-1.5 vs 5.8+/-1.1, p<0.001). No significant reduction was observed in duration of vasopressor or antibiotic therapy or in length of stay in the ICU. CONCLUSION: This study demonstrated that intensive blood glucose control is achievable using a nurse-directed nomogram. This improved control was achieved, regardless of diabetes status of the patient, without substantially compromising safety or increasing resource use.     

Management of acute iron overdose

Treatment of severe iron overdose in two children is described, and the pathophysiology of iron toxicity and management of acute iron poisonings are reviewed. An 11-month-old boy was comatose and in shock several hours after ingesting approximately 50 ferrous sulfate tablets (elemental iron 390 mg/kg). He had hyperglycemia and leukocytosis. Lavage was performed with a solution containing deferoxamine and sodium bicarbonate, and deferoxamine was given by continuous i.v. infusion for 48 hours. The initial serum iron (SI) concentration of 14,250 micrograms/dL decreased to 657 micrograms/dL nine hours after i.v. deferoxamine therapy was initiated. A roentgenogram showed tablets in the stomach and small bowel. Packed red blood cells were administered to treat apparent necrotizing gastroenteritis. SI concentration returned to normal by day three [corrected], and the child recovered. A 2.5-year-old boy was examined 1.25 hr after ingesting an estimated 55 tablets of ferrous gluconate 325 mg (elemental iron 130 mg/kg). Initial SI concentration was 134 micrograms/dL, and total iron-binding capacity (TIBC) was 219 micrograms/dL. A roentgenogram indicated iron concretion in the stomach and iron tablets in the small bowel. He underwent lavage with solution containing sodium bicarbonate. An i.m. dose of deferoxamine was administered, followed by i.v. deferoxamine therapy. SI concentration eight hours after the ingestion was 290 micrograms/dL, and whole-bowel irrigation was begun with polyethylene glycol-electrolyte solution. The irrigation and deferoxamine therapy were discontinued 20 hours after the ingestion, when SI concentration was 73 micrograms/dL, and the child recovered. Acute iron ingestions of more than 60 mg/kg are potentially serious. Patient 1 had severe iron intoxication, while aggressive treatment prevented severe toxicity in patient 2. Acute iron toxicity includes effects on the GI tract and the cardiovascular, metabolic, hepatic, and central nervous systems. Guidelines for assessing the severity of an overdose and selecting the most appropriate therapy are provided. The indications for chelation therapy with deferoxamine, gastric decontamination procedures including use of lavage solutions and whole-bowel irrigation, and adjunctive measures are described. Management of acute iron overdose includes supportive care, GI decontamination, and chelation therapy.     

Model-based insulin and nutrition administration for tight glycaemic control in critical care

OBJECTIVE: Present a new model-based tight glycaemic control approach using variable insulin and nutrition administration. BACKGROUND: Hyperglycaemia is prevalent in critical care. Current published protocols use insulin alone to reduce blood glucose levels, require significant added clinical effort, and provide highly variable results. None directly address both the practical clinical difficulties and significant patient variation seen in general critical care, while also providing tight control. METHODS: The approach presented manages both nutritional inputs and exogenous insulin infusions using tables simplified from a model-based, computerised protocol. Unique delivery aspects include bolus insulin delivery for safety and variable enteral nutrition rates. Unique development aspects include the use of simulated virtual patient trials created from retrospective data. The model, protocol development, and first 50 clinical case results are presented. RESULTS: High qualitative correlation to within +/-10% between simulated virtual trials and published clinical results validates the overall approach. Pilot tests covering 7358 patient hours produced an average glucose of 5.9 +/- 1.1 mmol/L. Time in the 4-6.1 mmol/L band was 59%, with 84% in 4.0-7.0 mmol/L, and 92% in 4.0-7.75 mmol/L. The average feed rate was 63% of patient specific goal feed and the average insulin dose was 2.6U/hour. There was one hypoglycaemic measurement of 2.1 mmol/L. No departures from protocol or clinical interventions were required at any time. SUMMARY: Modulating both low dose insulin boluses and nutrition input rates challenges the current practice of using only insulin in larger doses to reduce hyperglycaemic levels. Clinical results show very tight control in safe glycaemic bands. The approach could be readily adopted in any typical ICU.     

Evaluation of total-dose iron sucrose infusions in patients with iron deficiency anemia.

PURPOSE: The safety and efficacy of a total-dose iron sucrose infusion protocol used in a large, tertiary care teaching hospital were studied. METHODS: Nondialysis-dependent patients ages 18 years or older who received > or =250 mg of iron sucrose as a single i.v. infusion between January 2005 and January 2007 were eligible for study inclusion. The protocol for total-dose iron sucrose infusion was the same for all patients. The total dose of iron sucrose for each patient was calculated using an equation that included the desired hemoglobin (Hb) value, observed Hb level, ideal body weight, and sex. The calculated dose was divided into portions, rounded to the nearest 250 mg, and administered over four hours every other day. Outcomes measured included Hb, transferrin saturation, and serum ferritin values. RESULTS: A total of 26 patients met the inclusion criteria. The mean +/- S.D. Hb concentration before total-dose iron sucrose infusion was 9.37 +/- 0.9 g/dL, and the mean +/- S.D. corpuscular volume was 75 +/- 7.1 mum(3). The mean +/- S.D. postinfusion Hb concentration for 19 patients for whom follow-up Hb levels were available was 11.4 +/- 1.2 g/dL, significantly higher than the 9.45 +/- 0.8 g/dL measured before the first infusion (p = 0.03). No significant adverse effects were reported in 47 of 49 infusions, with 2 patients experiencing mild nausea. CONCLUSION: A treatment protocol consisting of alternate-day total-dose iron sucrose infusions was well tolerated and appeared to be effective in improving Hb concentrations in patients with iron deficiency anemia and without chronic kidney disease.     

In-hospital treatment of hyperglycemia: effects of intensified subcutaneous insulin treatment

ABSTRACT

Background: Hyperglycemia is common in hospitalized patients; however, glycemic control obtained during hospitalization is often suboptimal. No methods for achievement of proper glycemic control in this population have been validated in the in-hospital setting.

Aims: To study the effect of a novel intensive subcutaneous insulin protocol on the quality of in-hospital glycemic control.

Methods: Included in this prospective controlled study were all diabetic patients admitted to the internal medicine departments in a tertiary medical center during a 1-year period. The study was divided into pre-intervention (n = 94), intervention (n = 102) and post-intervention (n = 79) periods. During the intervention period all hospitalized diabetic patients with blood glucose >?200?mg/dL were treated with an intensive multi-injection protocol consisting of two or four times daily regular/NPH insulin injections.

Results: Mean glucose level throughout hospitalization was 178.7 ± 47?mg/dL in the intervention period versus 198.8 ± 60?mg/dL in the pre-intervention period (?p < 0.05). During the intervention period, the difference between mean admission and discharge day glucose levels was 43?mg/dL in patients treated with four times daily insulin injections, in contrast to no change noted in the other treatment groups. During the post-intervention period the rate of implementation of the intensive protocol by the internal medicine teams declined to 47.5%, in contrast to a 78.4% implementation rate during the intervention period. This decline was associated with deterioration of glycemic control.

Conclusions: The use of intensified insulin regimen improved the glycemic control of hospitalized diabetic patients. Successful incorporation of such intensive protocols into daily medical routines requires close involvement and continuous physician guidance by the hospital diabetes team.     

Effect of chlorpromazine on blood glucose and plasma insulin in man

Summary In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.     

T-1032, a cyclic GMP phosphodiesterase-5 inhibitor, acutely blocks physiologic insulin-mediated muscle haemodynamic effects and glucose uptake in vivo

1. Cyclic GMP phosphodiesterase-5 inhibitors have been shown to alter blood flow in specific tissues by potentiating local NO-dependent vasodilatory mechanisms. Since the haemodynamic effects of physiologic insulin, particularly capillary recruitment, may be critical for muscle glucose uptake in vivo and are blocked by inhibitors of nitric oxide synthase, we have explored the acute effects of the specific cGMP phosphodiesterase-5 inhibitor T-1032 on physiologic insulin action in anaesthetized healthy rats in vivo. 2. Whole-body glucose infusion (GIR), femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, and muscle cGMP were determined. The experimental groups were T-1032 (10 microg min-1 kg-1) infused for 1 h before and during a euglycaemic insulin clamp (3 mU min-1 kg-1 x 2 h), T-1032 infused for 3 h with saline, T-1032 during a 2 h clamp, T-1032 with saline for 2 h, and a 2 h saline control. 3. Insulin increased GIR from zero to 13 mg min-1 kg-1, HGU from 0.1+/-0.01 to 0.43+/-0.05 micromol min-1, R'g and 1-MX, marginally increased FBF, and had no effect on blood pressure or heart rate. T-1032 alone had no effect on blood pressure, heart rate, FBF, VR, HGU, R'g or 1-MX, but increased muscle cGMP. T-1032 1 h before and during insulin completely blocked GIR (1 h), HGU (2 h), R'g (2 h), and 1-MX (2 h). T-1032 commenced with insulin had only partial blocking activity against insulin. 4. We conclude that T-1032 is a potent acutely acting inhibitor of the muscle effects of physiologic insulin on capillary recruitment and glucose uptake in vivo. These, together with inhibition of whole-body glucose infusion during insulin, may caution against the use of isoenzyme-5-specific cyclic GMP phosphodiesterase inhibitors as therapeutic agents.     

Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding-scale insulin therapy

STUDY OBJECTIVE: To determine the efficiency and effectiveness of current prescribing practices relative to short- and intermediate-acting insulins in the prevention or treatment of acute hyperglycemic episodes in hospitalized patients with diabetes mellitus or hyperglycemia, and to identify clinical findings that influence the effectiveness of insulin therapy in these patients. DESIGN: Retrospective observational study. SETTING: University-affiliated hospital. PATIENTS: Ninety consecutive adult inpatients who had orders placed for as-needed subcutaneous regular or lispro sliding-scale insulin. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for patients' clinical characteristics and responses to administered insulin that were recorded during each of the first 5 days of hospitalization in which sliding-scale insulin therapy was used. Despite the immediate or bedside availability of both computerized and manual means to record finger-stick blood glucose levels and insulin injections, uncertainties or missing information related to execution, timing, blood glucose levels, or insulin dose were present in approximately 30% of all anticipated points of care involving insulin. Ten episodes of hypoglycemia in six patients were associated with sliding-scale insulin. Appropriately timed, successive glucose measurements documented a decrement in elevated blood glucose values to within the target range of 90-130 mg/dl after 76 (12%) of 621 sliding-scale insulin injections. Glucose levels remained elevated, and insulin effects were therefore subtherapeutic after 523 injections (84%). Despite blood glucose levels that remained persistently elevated, corresponding adjustments in either the timing or the dose of insulin were made infrequently. Sliding-scale insulin regimens were never adjusted in 73 patients (81%). Through 5 days of therapy, the proportion of patients who attained good glycemic control ranged from 2-10% (mean 6%). The mode of overall glycemic control was poor, with 51-68% of patients in this category on any given day. Overall, treated diabetic and hyperglycemic patients were more likely to be poorly controlled than relatively well controlled. CONCLUSION: Our findings reveal outcomes associated with sliding-scale insulin that are widely variable, often ineffectual, and prone to deficiencies in monitoring, documentation, and prescribing soundness. Efforts to improve glycemic control in hospitalized patients are clearly needed.     

What are the adverse effects of ethanol used as an antidote in the treatment of suspected methanol poisoning in children?

BACKGROUND: Ethanol used as an antidote is said to have various adverse effects, particularly in children. The rate of these adverse effects is not known. METHODS: Twenty-one-year retrospective chart review (1980-2000) from suspected methanol poisoning patients treated with ethanol in two large pediatric tertiary care centers. RESULTS: A total of 60 children (median age of 24 months) received ethanol for suspected methanol poisoning: 39 orally and 21 intravenously. Median initial methanol level was 4.16 mmol/L (13.3 mg/dL) (range 0 to 87.5 mmol/L or 0 to 280 mg/dL). Median duration of ethanol treatment was 16 hours (range 1.5 to 72 hours). None [0% (95% CI 0-5%)] of the 60 patients developed symptomatic hypoglycemia. Of the 50 patients that had a glucose level measured, none [(0% [95% CI 0-6%)] had a serum glucose concentration < 2.78 mmol/L (< 50 mg/dL). Eight patients [16% (95% CI 8-30%)] had at least one serum glucose concentration between 2.78-3.61 mmol/L (50-65 mg/dL), but none of those had symptoms compatible with hypoglycemia. A total of 42 patients [84% (95% CI 70-92%)] had all their serum glucose concentrations > 3.61mmol/L (> 65 mg/dL). There was no identifiable difference in the glucose intake between the serum glucose concentration groups. Six out of the 60 patients [10% (95% CI 4-21%)] were described as more drowsy after ethanol but none was comatose or needed intubation. No child showed signs of hypothermia [0/40 (95% CI 0-8%)] (rectal temperature < 35 degrees C), hepatotoxicity (0/12) (AST or ALT > 100 U/L) or even thrombophlebitis (0/21). None of the 22 patients with toxic levels of methanol (> or = 26.2 mmol/L- > or = 20 mg/dL) died or had ethanol-induced morbidity despite wide variation in ethanol levels. CONCLUSION: The rate of clinically important adverse effects related to ethanol used as an antidote to treat methanol poisoning in children was either absent or low in a tertiary care pediatric hospital setting. There was no morbidity or mortality associated with ethanol when it was used despite wide variation in ethanol levels. These results suggest that with appropriate monitoring and intravenous glucose intake in a controlled environment such as a pediatric intensive care unit, ethanol therapy does not carry as many risks as currently believed.