Which Insulin Can Be Administered by Continuous Intravenous Infusion
Side Effects of Drugs Annual 32
R.C.L. Page , in Side Effects of Drugs Annual, 2010
Continuous subcutaneous insulin infusion (CSII)
Methods of insulin delivery have been compared in a retrospective study in which two patients with type 1 diabetes treated with multiple-dose insulin injections (n = 60; mean age 29 years) were compared with each patient treated with CSII (n = 30; mean age 30 years) (14 c). There was an increased risk of neonatal hypoglycemia babies of those using CSII (11 versus 8; 36% versus 13%). The maternal risk of hypoglycemia was similar in the two groups, but ketoacidosis was more frequent in those who used CSII (4 versus 1; 13% versus 1.6%). Ketoacidosis was mild and due to mechanical failure of the pump. Thus there were potential problems with CSII in pregnancy, without apparent benefits.
In 50 patients with type 1 diabetes, mean age 13 years (26 women), who had used CSII for at least 6 months, common findings were scars of less than 3 mm (n = 47), erythematous subcutaneous nodules (21) and lipohypertrophy (22) (15 c). There was no difference between men and women. Two patients had required oral antibiotics for local infections and 13 patients had used topical antibiotics. Patients who used non-metal catheters inserted at 90° had fewer problems than those who had inserted them at smaller angles. BMI was negatively correlated with the severity of the skin changes. Skin infections were more common with CSII in earlier studies, and further studies looking at longitudinal changes and the effects of cannula insertion are required.
CSII has mainly been used by people with type 1 diabetes. In 382 patients with newly diagnosed type 2 diabetes, mean age 51 years, BMI 25 kg/m2, who were randomized to CSII, multiple daily injections or oral hypoglycemic drugs to achieve rapid normoglycemia, therapy was stopped after 2 weeks of achieving fasting blood glucose concentrations of less than 6.1 mmol/l and 2 hour postprandial glucose concentrations of less than 8 mmol/l (16 C). There were no episodes of severe hypoglycemia, but there was a non-significant increase in the number of episodes of minor hypoglycemia in those who used CSII (42 of 137; 31%) and multiple injections (35 of 124; 28%) compared with oral hypoglycemic drugs (23 of 121; 19%). Target blood glucose concentrations were achieved at a mean of 4 days in 133 of 137 patients who used CSII, 5.6 days in 118 of 124 who used multiple injections and 9.3 days in 101 of 121 who used oral drugs.
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A 45-year-old man with a family history of type 2 diabetes, who had had type 1 diabetes for 18 years, started using CSII, taking 85 units of insulin in a day, half of which was basal to control raised blood glucose concentrations (17 A). The dosage of insulin was gradually reduced to 43 units/day. There was no weight gain at 3 months (BMI 20.8 kg/m2), when blood glucose control was good. At 15 months his BMI had increased to 27 kg/m2 and his blood glucose control had deteriorated. He had hepatic steatosis. Metformin was added and improved his blood glucose concentrations.
The authors suggested that ease of management led to increased calorie intake, causing excessive weight gain, allowing him to develop features of type 2 diabetes. This is not specific to CSII and can be seen in those who use other insulin regimens.
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Adjunctive Pharmacologic Therapies in Acute Myocardial Infarction
Jonathan P. Man , ... Bodh I. Jugdutt , in Cardiac Intensive Care (Second Edition), 2010
Acute Phase
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Insulin infusion should be given to normalize blood glucose in STEMI patients with complicated courses (class I, evidence level B). Insulin infusion during the first 24 to 48 hours is reasonable for managing STEMI patients with hyperglycemia even in patients with an uncomplicated course (class IIa, evidence level B).
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Glucose control should be targeted at less than 180 mg/dL (<10 mmol/L) for all post-MI patients. Critically ill cardiac patients (cardiogenic shock) may benefit from even further aggressive control of glucose to less than 140 mg/dL (<7.8 mmol/L).
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Diabetes Mellitus
Mark A. Sperling , ... Moshe Phillip , in Sperling Pediatric Endocrinology (Fifth Edition), 2021
Insulin Pump Therapy
CSII delivered by pumps of varying degrees of sophistication have become a standard means of treatment for children with diabetes. Some of the practical benefits of CSII compared with MDI are listed in Box 21.8. A specific risk of pump therapy is that prolonged accidental or purposeful interruption of insulin delivery over several hours can lead to the development of ketones and DKA because the patients are only receiving rapid-acting insulin. 329 This risk can be reduced or eliminated by regular blood glucose testing and to facilitate blood glucose testing, a variety of devices have been developed. Linking these devices with pumps and algorithms led to the emergence of autoregulated insulin delivery systems, which are constantly improving and becoming incorporated into daily practice as detailed later.
A recent ISPAD guidelines chapter focuses on diabetes technology. 330
Ideal candidates for pump therapy include motivated families who are committed to monitoring blood glucose at least 4 times per day and have a working understanding of basic diabetes management, especially carbohydrate counting and using ICR and ISF to calculate insulin doses.
Most currently available insulin pumps are "smart" pumps into which both ICRs and ISFs are programmed to create a bolus calculator. Some pumps have the ability to receive and integrate blood glucose values into their bolus calculator through a wireless link with a specific blood glucose meter. Bolus doses can be administered over a few minutes or as square-wave and dual-wave boluses over a longer period of time. Ideally, bolus doses should be delivered 10 to 15 minutes before the meal to minimize postmeal excursions. 331 In young children and picky eaters, a small priming bolus of insulin can be given before the meal to cover glucose levels above the target and the amount of carbohydrate that will be eaten reliably, followed by additional bolus doses depending on how many carbohydrates are actually consumed.
Basal insulin needs are covered by the rapid-acting insulin, which is delivered through a preprogrammed "basal pattern." This pattern can be made up of multiple different rates, which allow for a waxing/waning pattern of basal insulin delivery. In addition, most pumps allow for multiple 24-hour basal patterns to be preprogrammed and stored in the memory. For example, some adolescents have a basal pattern for school days and one for weekends to account for their tendency to wake up much later on weekends and holidays. Finally, temporary changes can be made to the basal insulin pattern, which can be an effective tool for dealing with exercise or sick day management.
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Perioperative Management of Endocrine Disorders
KEVIN FURLONG DO , ... SERGE JABBOUR MD , in Medical Management of the Surgical Patient (Third Edition), 2008
Continuous Intravenous Infusion Therapy
Intravenous insulin infusion has many advantages over the subcutaneous route in the surgical patient. Its rapid onset of action and ease of titration allow for rapid control of hyperglycemia. This makes it the method of choice in patients with rapidly changing insulin requirements. This approach is also beneficial in patients with significant subcutaneous edema or impaired perfusion of subcutaneous sites. The medical literature supports the use of continuous intravenous insulin infusions for many clinical indications. Indications that have a high level of evidence include diabetic ketoacidosis and nonketotic hyperosmolar state, critical illness, myocardial infarction or cardiogenic shock, and the postoperative period after cardiac surgical procedures. Indications that have a weaker level of evidence with respect to outcome data include patients with type 1 diabetes who are NPO, general perioperative care including organ transplantation, TPN, hyperglycemia during high-dose corticosteroid therapy, stroke, and use as a dose-finding strategy anticipatory to initiation of subcutaneous insulin therapy in type 1 or type 2 diabetes.
In their consensus conference, the American College of Endocrinology and the American Association of Clinical Endocrinologists recommended evidence-based glycemic thresholds for initiating intravenous insulin infusion therapy [
Many different intravenous insulin administration protocols are available. Furthermore, glycemic targets may differ based on pragmatic considerations such as patient-to-nursing ratios and staff education. In general, regular insulin is typically mixed in a 1:1 ratio with 0.9% saline solution, and the infusion is given as a piggy back with other intravenous fluids. Frequent blood glucose monitoring is performed, and adjustments to the insulin infusion rate are made according to the hospital protocol.
Conversion from intravenous insulin infusion to subcutaneous insulin therapy should be attempted only after the patient's clinical status has stabilized; more specifically, the patient is no longer critically ill, is not receiving volume resuscitation and pressors, and has stabilized nutritional requirements. The patient's 24-hour insulin requirement can be estimated by extrapolating the average hourly rate necessary to achieve the goal serum glucose in the most recent 6- to 8-hour period. Eighty percent of the 24-hour requirement is then divided equally into basal and nutritional insulin. For example, suppose a patient has been maintained in the target glycemic range for the past 6 hours on an average of 2 U/hour. The total 24-hour requirement for that patient is 2 U/hour × 24 hours = 48 U of insulin. One then multiplies this number by 80%, which equals 38 U when rounding to the nearest unit. Therefore, 19 U would be given as basal insulin, and 19 U would be given throughout the day as nutritional or prandial doses.
When transitioning from continuous intravenous insulin infusion to subcutaneous insulin therapy, the first dose of subcutaneous insulin must be given before the intravenous insulin is stopped. If administering rapid-acting or short-acting insulin, one should wait 15 to 30 minutes before discontinuing the infusion. If intermediate-acting or long-acting insulin is given, one should wait 2 to 3 hours before discontinuing the insulin infusion.
A minority of patients receiving insulin infusions will not require standing subcutaneous doses of insulin on discontinuing the infusion. These patients typically have type 2 diabetes or stress-induced hyperglycemia and tend to require less than 0.5 U/hour of insulin.
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Treatment of Type 1 Diabetes Mellitus in Adults
Ravi Retnakaran , Bernard Zinman , in Endocrinology (Sixth Edition), 2010
Continuous Subcutaneous Insulin Infusion
The external insulin infusion pump was first developed in the late 1970s, providing the basis for modern continuous subcutaneous insulin infusion (CSII) therapy. 96 With CSII, an external infusion pump delivers a continuous infusion of rapid- or short-acting insulin through a catheter inserted into the subcutaneous tissue of the abdominal wall. The pump is preprogrammed by the patient to deliver insulin continuously at a specified rate that is designed to meet the individual's basal insulin demands. For meal coverage, patients use the pump to deliver a specified bolus of insulin before eating. The rapid-acting insulin analogues are the insulins of choice in CSII, as both lispro and aspart have been shown to reduce postprandial glycemia, A1c concentration, and the incidence of hypoglycemia compared with regular insulin in this setting. 97-99
CSII offers advantages over MDI therapy in terms of convenience and flexibility. Because the continuous infusion provides basal insulin at all times, the timing of meals with CSII, unlike with MDI, is completely flexible. At any given time, the rate of basal infusion can be adjusted immediately—an option that is not available with MDI. Moreover, current insulin pumps have multiphasic basal settings, allowing the user to set varying rates of basal insulin replacement at different times of the day depending on requirements. For instance, the pump can be preprogrammed to increase the basal rate of insulin infusion in the early morning hours in patients in whom the physiologic early morning secretion of growth hormone otherwise would lead to hyperglycemia (the "dawn phenomenon"). In addition, many insulin pumps have programing capabilities that facilitate dose selection for carbohydrate counting and insulin correction boluses.
The major limitation with CSII is the significant cost associated with the pump and necessary supplies, such as the tubing, which must be changed every 48 to 72 hours. Another disadvantage is the risk for infection at the insertion site of the catheter. Catheter site infections occur at an estimated rate of 7.3 to 11.3 events per 100 years of patient follow-up. 20,100 These infections usually are readily treatable with antibiotics and a change of insertion site. In rare cases, a subcutaneous abscess requiring surgical drainage can develop. Finally, interruption of basal insulin delivery due to pump malfunction or catheter disruption can rapidly lead to hyperglycemia or even ketoacidosis, as patients will quickly become markedly insulinopenic owing to the use of only rapid- or short-acting insulin in CSII. 101
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Management of gestational diabetes mellitus to optimize outcomes
Yoel Toledano , ... Moshe Hod , in Obesity and Obstetrics (Second Edition), 2020
New technologies
Continuous subcutaneous insulin infusion (CSII), or insulin pump, is an alternative treatment to multiple daily injections for women with type 1 diabetes mellitus [96]. However, only rarely it is used in patients with GDM. One of the potential scenarios, where CSII may be effective, is a woman with early onset GDM and a very high insulin resistance. However, it should be studied carefully.
Another new technology that was evaluated during pregnancy, mainly in women with type 1 diabetes (CONCEPTT study, [97]), is continuous glucose monitoring system. The evidence in women with GDM is scarce.
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Insulin
In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016
Treatment
In 95% of cases the local reactions disappear spontaneously. A switch to less immunogenic, highly purified insulin, or insulin lispro [187], is necessary if the reactions persist. For local allergic reactions, antihistamines or the addition of hydrocortisone 2 mg along with the insulin are seldom needed. Hydrocortisone suppresses local allergic reactions. For generalized reactions, skin testing is often necessary to establish allergic desensitization. One should start with low intradermal doses and, if necessary, add hydrocortisone.
For therapy of local lumps, extravasation, etc., one should first seek to improve the injection technique. Substitution with highly purified insulin is recommended. Injection with purified insulin into the affected area may speed up resorption of the lumps. Lipodystrophy or lipoatrophy improve after switching to highly purified human or insulin lispro. Lipohypertrophy, on the other hand, often fails to respond to changes in the insulin regimen [188]. Varying the injection site may help, but differences in absorption rate then have to be taken into account.
Insulin resistance is said to be present when more than 200 U/day have to be injected; it is generally due to insulin antibodies. In general, antibody titers fall when highly purified insulins are used, but they sometimes persist after the switch. Some diseases, such as infections, endocrine hyperfunctional states (acromegaly, Cushing's syndrome, thyrotoxicosis), leukemia, or stress, can contribute to insulin resistance. Recombinant IGF-I (insulin-like growth factor I), which has a structure comparable to insulin, may help to overcome insulin resistance [189]; adverse reactions are burning at the injection site, hypoglycemia, fluid retention, facial edema, increased heart rate, arthralgia, myalgia, parotid gland tenderness, and dyspnea.
Continuous subcutaneous insulin infusion with fast-acting insulin has been used in two cases.
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A 43-year-old man with type 1 diabetes developed local pruritus, redness, and swelling 4–5 times a week, 15–20 minutes after an injection, subsiding within 1–2 hours [190]. Later he had a generalized urticarial reaction 5 minutes after an injection. Insulin lispro did not help. When checked for allergens, he was positive for all types of insulin and negative for additives. With oral mizolastine the local reactions abated for a week, but then reappeared with every injection. Generalized urticaria recurred later. With continuous subcutaneous insulin infusion the local reactions immediately disappeared and metabolic control was improved.
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A 79-year-old man used mixed insulin for 2 months and developed swelling at injection sites, lasting 48 hours [191]. The lesions persisted despite switching to various types of insulin. He was allergic to insulin, as shown by a raised eosinophil count, a markedly increased IgE concentration, and antibodies to human, bovine, and porcine insulins in the RAST test. He was not allergic to needles or additives. With subcutaneous bolus doses of insulin lispro and Humulin he developed induration and wheal-and-flare reactions. When hydrocortisone 10 mg was added to each injection, the allergic reactions disappeared, but they recurred after 2 months. With continuous subcutaneous insulin infusion there were no allergic responses for 3 months. His raised IgE concentrations fell.
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Insulin Pumps and Artificial Pancreas
Nadine Taleb , ... Rémi Rabasa-Lhoret , in Encyclopedia of Endocrine Diseases (Second Edition), 2019
CSII Related Adverse Events
The use of CSII is associated with a number of adverse events despite the progress in this technology and can be categorized into perfusion site or catheter problems, cutaneous reactions, metabolic adverse events, and pump software problems. These adverse events are common and can occur in 40% of users per year but they necessitate hospital admissions only in very rare cases (Ross et al., 2015 ). The most serious adverse events are related to metabolic control, particularly diabetic ketoacidosis that can result from perfusion site/catheter failure and prolonged insulin infusion interruption ( Ross et al., 2015). In a recent online survey including adult patients and examining their perceptions about CSII use, the majority of participants perceived it positively, reporting improvements in glucose control without compromising their quality of life. However, technical issues related to perfusion site, catheter and cutaneous problems were quite common with only 3% of patients reporting no problems of any kind in the past year of use (Nadine Taleb et al., 2017a). Other major issues with CSII are the need to carry the pump at all times as well as associated costs (significantly higher than MDI) leading to limited access and coverage in a lot of countries.
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A worldwide yearly survey of new data in adverse drug reactions and interactions
R.C.L. Page , in Side Effects of Drugs Annual, 2014
Insulin glulisine
Insulin glulisine CSII has been compared with insulin aspart and insulin lispro for 13 weeks in 256 patients with type 1 diabetes (mean age 44 years, 53% women) in three different orders (glulisine→aspart→lispro or aspart→lispro→glulisine or lispro→glulisine→aspart) [22 C]. Hypoglycemia was more common with insulin glulisine: 74 events per patient year compared with 65 with insulin aspart and 63 with insulin lispro. This was particularly apparent early after crossover.
When insulin glulisine 0.2 IU/kg was compared with insulin lispro in 20 healthy Chinese men using hyperinsulinemic euglycemic clamps, the AUC0→1h for the glucose infusion rate was significantly greater with glulisine (69 mg/kg versus 50 mg/kg) [23 c]. The overall AUCs for each insulin were similar. Thus, the pharmacodynamics of insulin glulisine are slightly different to those of insulin lispro when injected subcutaneously in the abdomen, and this may need to be considered when calculating doses.
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Existing and Potential Applications of Glucose Prediction Models
Eleni I. Georga , ... Stelios K. Tigas , in Personalized Predictive Modeling in Type 1 Diabetes, 2018
9.1.1 Components of Artificial Pancreas Systems
CGM, CSII, and control algorithms constitute the backbone technologies of current systems of closed-loop control of glucose concentration in type 1 diabetes or, the so-called artificial pancreas (AP) systems, being meticulously combined to emulate the feedback glucose-responsive functionality of beta-cells in normal physiology of glucose metabolism [7]. Fig. 9.1 illustrates the main components of an AP system. Interstitial glucose concentration measurements are the main input of the controller which, depending on the underlying algorithm, determines the insulin delivery rate such that euglycemia is safely achieved and maintained. Additional bio- and physiological signals (e.g., galvanic skin response, heart rate variability, skin temperature, energy expenditure), predictive or reflective of glycemia as well as patient's physiological, emotional, and behavioral status, may be exploited in order to adjust the operating mode of the controller [11,12].
Figure 9.1. Components of closed-loop controller of glucose in type 1 diabetes based on the double subcutaneous route (CGM, CSII).
The main algorithmic approaches to closed-loop control in type 1 diabetes rely on proportional-integral-derivative (PID) control and model predictive control (MPC), where the proper tuning of the control algorithm's parameters determines its sensitivity to hypoglycemic or hyperglycemic excursions [13,14]. In addition, fuzzy logic theory [15,16] and mathematical models of β-cell physiology [17] have been also successfully applied to regulating blood glucose. Most importantly, the degree of system's automation, and subsequently, the sophistication of the overall control algorithm, depends on the management of external disturbances to the glucose system (e.g., meals, exercise) [11,12]. For instance, the hybrid closed-loop approach employs meal announcement or manual prandial insulin bolus delivery, which may lessen the effect of the intrinsic delays imposed by the double subcutaneous route and, therefore, mitigate the risk of postprandial hyperglycemia or late-onset postprandial hypoglycemia [18]. More elaborate AP approaches may involve automatic food recognition and quantification of the nutrient content of meals by properly combining image processing, computer vision and machine-learning technologies [19,20]. Moreover, the functionality of the controller may be supported by hypoglycemia risk minimizing modules, i.e., threshold-based insulin pump interruption or predictive low-glucose-insulin suspension [21]. A three-layer modular architecture for closed-loop control in type 1 diabetes has been proposed which separates functionalities assuring patient's safety (e.g., hypoglycemia prevention) from real-time customizable (e.g., body weight, insulin-to-carbohydrate ratio, and basal insulin delivery) MPC of basal insulin rate [22]. To this end, bihormonal AP systems adopt a more holistic approach, regulating glucose homeostasis by subcutaneously delivering both insulin and glucagon hormones aiming at hypoglycemia prevention or counteregulation [7,23,24].
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