Implementing an intravenous insulin protocol in your practice 347medical professions caring for the patients and hospital ad- Realistic Goalsministrative staff. Successful implementation of hospital- One of the major pitfalls in implementing any protocol is towide tight glycemic control will take the form of treatment set unrealistic glycemic goals. If the current baseline averagealgorithms, which advocates a stepwise approach toward eu- blood glucose for patients with diabetes is well over 200glycemic goals and appropriate blood glucose monitoring of mg/dL (11 mmol/L), then it is unrealistic to achieve the ACE/these patients. ADA recommended goals as a ﬁrst step. It would be a safer and more easily accepted strategy to implement a stepwise approach, starting with an initial blood glucose goal of lessIdentiﬁcation of Barriers than 200 mg/dL, and then progressively stepping down theThe barriers to implementing an insulin infusion protocol goal as experience and comfort are gained. The Portland Pro-both in the intensive care unit and on nonintensive care tocol is one that has been speciﬁcally designed with thisﬂoors are numerous. In fact, implementation of an intrave- stepwise implementation process in mind. This widely usednous insulin protocol in the non-ICU setting may be partic- protocol is available at ﬁve different target blood glucoseularly strewn with administrative, political, nursing, and ranges with separate protocols at each target range availablemedical challenges, despite the fact10 that doing so is para- for both the ICU and the non-ICU settings. These can bemount to clinical outcomes success. (See Furnary & Wu, pp. freely downloaded at www.portlandprotocol.org. The rec-302-308.) Some of these are simply educational opportuni- ommended time to move to a lower target range is when theties, as barriers include safety concerns, such as fear of hypo- mean blood glucose obtained for all patients on the current particular protocol crosses below the next upper target limit.glycemia, insufﬁcient nursing staff to patient ratios, lack of For example when the mean blood glucose of all patients soadministrative and physician support, various system and treated is 175 mg/dL, then it is time to move from a targetprocedural issues, and the subjective human resistance to range of 150 to 200 mg/dL to a target range of 125 to 175change. mg/dL. Before implementing an intravenous infusion protocol, it In addition to the target blood glucose, one must consideris imperative that current diabetes-related practices in the the patient population. It will be easier to convince colleaguesinstitution are evaluated and critical questions are addressed. and staff of the importance of implementing an insulin infu-What is the current level of glycemic control? Who is check- sion protocol for a patient population such as cardiac sur-ing patients’ blood glucose? How frequently is it being gery, post-myocardial infarction, or surgical intensive carechecked? How supportive are medical staff and nursing ad- because the beneﬁts have been clearly established in the lit-ministration for improving glycemic control? What educa- erature. Once you have success in your institution with thesetional mechanisms exist for disseminating published clinical populations, it will make it easier to move out to other pop-information to the nursing staff so that they fully understand ulations as well. Another important factor to consider is thethe clinical rationale for tight glycemic control? What are the locations where insulin infusions can be safely used in theexisting institutional rules and regulations regarding phar- institution. Starting on units already familiar with the use ofmacological intravenous infusions in the non-ICU setting? insulin infusion protocols will improve success and can beThis will allow for identiﬁcation of the unique barriers of the used to gather support for moving to other areas within theinstitution. institution.Strategies for Selection of an Insulin Infusion ProtocolOvercoming Barriers Several insulin infusion protocols have been validated in practice and published in the literature.8,9,14-17 They rangeKey steps to overcome the barriers include building support from the simple to the very complex, and the glycemic goalswith multidisciplinary champions, involving key staff in the for these protocols are equally variable depending on theprocess, educating staff and administrators of the beneﬁts of established glycemic goals at the time they were developed.improving glycemic control, and internally marketing the The ideal insulin infusion protocol is based not only on theclinical success of the protocol. Additional caveats for success current blood glucose, but also on the rate of change in bloodinclude starting with higher blood glucose targets, starting glucose and the insulin sensitivity of the patient. In addition,with a proven patient population (ICU or CCU), and using an the protocol should be easy to implement and have clear andestablished insulin infusion protocol that has already been speciﬁc directions for titration, blood glucose monitoring,validated for safety and efﬁcacy. Perhaps the most important and treatment of hypoglycemia. Many institutions developbarrier-breaking strategy is repeated education of the medical their own insulin infusion protocol, which requires expertise,and nursing staff. This empowers those in the trenches of time, and validation of safety and efﬁcacy.glycemic control with the multitude of published clinical Choosing a published insulin protocol that has alreadydata on the subject (such as those presented in this issue of been validated allows for more rapid implementation, with-Seminars). They thus learn that what they are doing is not just out the need for IRB approval. Table 1 compares some of theabout blood glucose control, but is actually about reducing key features of various published insulin infusion protocols.morbidity, mortality, and cost! Some of these protocols are quite complex and rely heavily
348Table 1 Key Features of Published Insulin Infusion Protocols Characteristics DIGAMI8 Van den Berghe9 Portland Protocol5,6 Krinsley Protocol14 Yale Protocol11 UWMC Protocol13SCTVS page reference 326-329 309-316 302-308 317-325 Not included Not includedPatient population Acute MI Adult surgical Cardiac surgery Medical and non- Adult medical Adults (excluding obstetrical) cardiac surgicalLocation of use CCU ICU ICU and non-ICU telemetry ICU ICU Throughout the hospitalTarget (Goal) Blood 125–180 mg/dl 80–110 mg/dl 150 –200 mg/dl (1992-1998) <140 mg/dl 100–139 mg/dl 80–180 mg/dl Glucose (BG) range 125–175 mg/dl (1999-2000) 100 –150 mg/dl (2001-2003) 80 –120 mg/dl (CVICU 2004) 70 –110 mg/dl (CVICU 2005)Frequency of BG Hourly until stable in Hourly until stable in target Every 30–60 minutes initially Hourly Hourly until stable in Hourly until stable in target monitoring target range then range, then decrease to every with speciﬁc parameters to target range, then range, then decrease to decrease to every 2 2 and eventually every 4 decrease to every 2 hours decrease to every 2 every 2 and eventually hours and less hours. once patient is stable in and eventually every 4 every 4 hours. frequently during the target range hours. night.Time to reach target BG 75% patients were Data not available 90% within Target range by 3 Data not available Mean of 10.1 ؎ 4.6 hrs 3.5 ؎ 0.3 hrs (critical care) range within goal range hours 3.9 ؎ 0.5 hrs (non-critical within 6 hours care)Glycemic control results Mean BG at 24 hrs Mean AM fasting blood glucose Average composite 3-day Mean BG was 52% of patients were Patients were hyperglycemic was 170 ؎ 53 mg/dl. was 103 ؎ 19 mg/dl. blood glucose (3-BG) was 130 ؎ 55 mg/dl. stable in the goal (BG>180 mg/dl) for 15% 121 ؎ 20 mg/dl for 2005. range, with 93% (critical care) and 18% (ICU and Ward) achieving a clinically (non-critical care) of the acceptable glycemic time they were receiving range (80–199 mg/dl). insulin infusion therapy.Hypoglycemia deﬁnition Hypoglycemia (BG<55 Hypoglycemia (BG<40 mg/dl) Hypoglycemia (BG<60 mg/ Hypoglycemia (BG<40 Hypoglycemia (BG<60 Hypoglycemia (BG<40 mg/ & rate mg/dl) occurred in occurred in 5.1% of patients. dl) occurred in 1.5% of all mg/dl) occurred in mg/dl) occurred in dl) Occurred in: 3.6% in 17.8% of patients. patients 1.88% of all 23% of patients critical care 4% in non- patients. critical careOutcome results Use of intensive Reduced ICU and hospital Decrease in hospital Hospital mortality was Clinical outcomes not Clinical outcomes not metabolic control mortality by over 30%. Also mortality by 65% and reduced 29.3% evaluated evaluated with insulin-glucose reductions in length of ICU reduced the incidence of infusion followed by stay, ventilatory support, deep sternal wound by subcutaneous renal replacement therapy, 63%. Decrease in length J.L. Kelly, I.B. Hirsch and A.P. Furnary insulin reduced sepsis, and critical care of stay by 2.0 days mortality at 1 year. neuropathy. One life was saved for every 9 patients treated.Insulin titration Done according to Done by a team of specially Done according to protocol Done according to Done according to Done according to protocol protocol by bedside trained nurses with by bedside nurses. protocol by bedside protocol by bedside by bedside nurses. nurses. assistance of physician. nurses. nurses.
Implementing an intravenous insulin protocol in your practice 349on clinical judgment, while others are simpler and easier to The protocol is divided into four columns based on insulinimplement in clinical practice. Three protocols, which the sensitivity. The ﬁrst column is for the most insulin-sensitiveauthors feel are sufﬁciently detailed to allow for implemen- patients, and the fourth column is for patients with the great-tation in clinical practice with minimal physician involve- est insulin resistance. The majority of patients start with thement in titration decisions, are described in more detail be- ﬁrst algorithm or column. Insulin-resistant patients, such aslow. those undergoing coronary artery bypass grafting, receiving a The Portland Protocol is a very effective protocol that has transplant, requiring glucocorticoids; or who receive greaterbeen used safely and effectively in a large number of open- than 80 units per day of insulin as outpatients, start withheart surgery patients in both critical care and telemetry set- algorithm 2. The insulin infusion rate is determined by thetings. This protocol has been in use since the early 1990s with patient’s current blood glucose and varies hourly until thea gradual decrease in the target blood glucose range. When patient is stable in the target range. If blood glucose targetsinitially implemented in 1991 the target blood glucose was are not achieved or if the blood glucose has not decreased by150 to 200 mg/dL (8.2 to 11 mmol/L). In 1999 the target at least 60 mg/dL in the preceding hour, the patient is movedblood glucose was reduced to 125 to 175 mg/dL (6.9 to 9.6 up to the next algorithm. Patients move down to a less ag-mmol/L) and then again in 2001 to 100 to 150 mg/dL (5.5 to gressive algorithm only if they experience hypoglycemia, de-8.2 mmol/L). A current Portland Protocol (version 2007.1) ﬁned as a blood glucose level of less than 60 mg/dL (3.3for the ICU with a goal blood glucose range of 80 to 120 mmol/L), or have two subsequent hourly blood glucose levelsmg/dL is reproduced in Appendix 1 (Portland Protocols at var- less than 70 mg/dL (3.8 mmol/L).ious target ranges are freely available for download at www.portlandprotocol.org). Education and Empowerment of Staff The Portland Protocol is usually started during the surgical Another important pitfall to avoid is the lack of sufﬁcient andprocedure. The protocol may be started the day before sur- continual staff education. Staff must understand that they aregery if the patient is hospitalized and is found to have a blood not just “ﬁxing” an elevated blood glucose level, but reducingglucose level greater than 180 mg/dL. The Portland Protocol morbidity, mortality, and cost. Without continual remindersis maintained in all cardiovascular ICU patients throughout of this, staff may lose sight of the value of improving glycemictheir stay in that unit. The Portland Protocol is then contin- control. No insulin infusion protocol can be safely imple-ued at least until 7 AM of the third postoperative day in mented without ensuring that staff is knowledgeable in howpatients who have left the intensive care unit and have gone to use it. The best educational approach is a varied one thatto the telemetry ﬂoor. The initial infusion rate is determined allows for different learning styles and different work sched-by the patient’s initial blood glucose and whether the patient ules and is repeated at frequent intervals to compensate forhas Type 1 or Type 2 diabetes. For patients substantially staff turnover. At UWMC we use a four-pronged approach.above target range, insulin boluses are used in addition to We started with diabetes education days, which are a combi-increased infusion rate. Blood glucose is monitored by ﬁnger nation of didactic lectures and discussion sessions regardingstick method or arterial line samples every 30 to 60 minutes the theory, rationale, and practical management of patientsuntil stable, after which the frequency of blood glucose test- with diabetes. These sessions are done on a voluntary basising can be reduced. This is a very efﬁcient protocol with 90% away from direct patient care. Staff that completed these ses-of patients reaching target range within 3 hours, largely due sions then assist with the second prong, which are smallto the use of IV bolus insulin concomitant with increases in in-service case studies done for each shift on the nursinginfusion rates. stations periodically. These case studies are also available in The Yale Protocol was developed for medical intensive care an interactive Powerpoint™ presentation for staff memberspatients with a goal blood glucose range of 100 to 139 mg/dL that are unable to attend an in-service session or want a(5.5 to 7.6 mmol/L) (Appendix 2).14 The initial bolus and review. The third prong is the availability of diabetes special-infusion rate are determined by dividing the patient’s current ists that are available via pager for questions. The fourth andblood glucose (eg, 350 mg/dL) by 100, to give a bolus dose ﬁnal prong is a mandatory competency examination to en-and rate of infusion (eg, 3.5 unit bolus with an infusion rate sure that staff can safely care for a patient on the insulinof 3.5 units per hour). Blood glucose is monitored hourly infusion protocol. Each institution will have unique educa-until the patient is stable within the goal blood glucose range. tional needs and thus the plan will differ, but education is aSubsequent insulin infusion rates are determined by the cur- key component of a successful insulin infusion protocol.rent blood glucose and the rate of change using multipletables. Using this protocol, the mean time to achieve targetblood glucose levels was 10.1 Ϯ 4.6 hours with nurse-to- Fear of Hypoglycemiapatient ratios of 1:1 or 1:2. Another potential pitfall with implementation of an aggres- The University of Washington Medical Center (UWMC) sive insulin infusion protocol is the risk of hypoglycemia andinsulin infusion protocol was developed for use in all adult possible morbidity associated with it. The best way to avoidpatients, surgical and medical, but excluding obstetrical pa- this is to mandate frequent blood glucose monitoring withintients, in both critical care and noncritical care settings (Ap- the protocol itself, have a clear and speciﬁc deﬁnition ofpendix 3).15 It is a column-based protocol, which was hypoglycemia, and have speciﬁc nursing orders for the treat-adapted from the protocol by Markovitz and coworkers.16 ment of hypoglycemia. This allows the nurse to rapidly treat
350 J.L. Kelly, I.B. Hirsch and A.P. Furnarya hypoglycemic event before any neurologic sequelae or mor- process speaks to the importance of the slow and steadybidity occurs. Of course mandating does not guarantee com- approach.pliance, and it is more important to make sure that it is The future of this concern and of glycemic control in gen-practical for staff to monitor the blood glucose as prescribed. eral is quite exciting due to the introduction of real-time Many hospitals restrict intravenous insulin infusion use to continuous glucose sensors for outpatient use in 2006. Clin-critical care units, because they perceive them as dangerous ical trials in the hospital are lacking, but the potential toand requiring close patient monitoring. They falsely believe provide near-normal glucose control with an extremely lowthat intravenous infusions are more risky than subcutane- risk of hypoglycemia could revolutionize the management ofously administered insulin, when in reality they are safer with hyperglycemia in the hospital.appropriate monitoring. The onset of action of intravenousinsulin is a mere minutes with a duration of action of onlyabout an hour. In contrast subcutaneous insulin has a much Financial Impactslower onset, but its duration of effect can be prolonged and In this day and age of rising awareness and concern aboutunpredictable in acutely ill patients. There are numerous re- escalating hospital costs, one of the major pitfalls to imple-ports in the literature of prolonged and severe hypoglycemia mentation of an intravenous infusion protocol may be thewith overdose of subcutaneous insulin, including the rapid- additional ﬁnancial cost of that therapy to the hospital itself.acting analogues.18,19 Permanent neurologic sequelae associ- Hospital and nursing administrators are less likely to widelyated with hypoglycemia has been linked to repeated and accept clinically effective protocols that overutilize hospitalprotracted episodes of hypoglycemia, rather than a single resources and nursing time without a ﬁnancial return on thatepisode, which is rapidly corrected. Subcutaneous (SC) in- investment. However, if ﬁnancial as well as clinical beneﬁtssulin can have as much as a 35% variability within the same can be shown, then all parties—patients, physicians, nurses,patient, while intravenous insulin is extremely predictable.20 and hospitals—will derive a beneﬁt and the protocol will beDue to the short pharmacokinetics and pharmacodynamics enthusiastically accepted. To date, three studies have exam-of intravenous insulin, blood glucose has been shown to be ined the cost-beneﬁt ratio for improved glycemic control insafely titrated in a non-ICU setting.15 Adequate monitoring the hospital setting in ﬁnancial terms.22-24 (See also Hilleman,must be performed for patients receiving an intravenous in- pp. 359-365.)fusion, yet ideal frequency is not known. Paradoxically, over- During the course of the Portland Diabetic project themonitoring is a major concern with SC insulin due to the long in-hospital cost for subcutaneous insulin injections given ev-pharmacodynamics of SC insulin, resulting in “insulin stack- ery 4 hours was compared with those of continuous intrave-ing.”21 nous insulin therapy. In this analysis not only were the direct Decisions that revolve around an institution’s choice of costs of insulin, syringes, intravenous bags, tubing, and glu-glucose monitoring equipment are also important. Are there cometer strips taken into account, but the all-important in-sufﬁcient glucometers available, and are they strategically direct costs of nursing time and pharmacy time were evalu-located to eliminate the need for staff to search for them when ated as well. Indirect costs were assessed by directly timing ofthey need one? Is the blood glucose monitor easy to use? Does all nursing and pharmacist components of both subcutane-it provide rapid and reliable results? Do staff members know ous and intravenous therapies. In this manner detailed hos-how to use it? If someone other than the bedside nurse is pital cost information was obtained.checking the blood glucose, are the results communicated in It was determined that the overall direct and indirect costsa timely manner? Attention to all of these questions and ed- for 3 days of subcutaneous insulin therapy averaged $32 perucating staff of the importance of following the prescribed patient. In comparison, cost of a full 3-day implementation offrequency of blood glucose monitoring are important to en- the Portland Protocol, with its frequent BG checks and infu-sure compliance. sion changes, cost the hospital $170 per patient. The ques- Another important consideration surrounds documenta- tion that then remains is “Does the ﬁnancial beneﬁt to thetion of glucose and insulin infusion data. Where will blood hospital exceed the extra $138 spent per patient on 3 days ofglucose levels be documented? How, when, and where will IV insulin therapy?” This question can be answered for bothinsulin infusion rates be recorded? Will blood glucose data be the hospital itself and the health care system as a whole.graphed? Streamlining this process will improve compliance, In terms of hospital savings the Portland Protocol reducedsimplify the evaluation the glucose trends, and contribute to both the incidence of deep sternal wound infection (DSWI)timely therapeutic decisions. Ideally this data should be and the length of stay (See Furnary & Wu, pp. 302-308).tracked in a computerized system at the bedside that can Comparison of the total hospital costs in that study revealeddisplay data in various ways depending on the user’s prefer- that the additional incremental cost of a hospital stay for aence. However, in the absence of a bedside electronic medical cardiac surgery patient who contracted a DSWI on the samerecord, organized metabolic data sheets should be used. The admission following open heart surgery averaged $24,600Portland group makes theirs available for download at port- more than that of similar patients who did not get a DSWI.landprotocol.org. Having the blood glucose data available in Overall DSWI rates in that study have been reduced to thethis manner will aid physicians in transitioning patients to current (2002 to 2005) rate of 0.3% with three full days of thesubcutaneous insulin or other therapies when clinically indi- Portland Protocol.cated. The complexity of each step of the implementation The meta-analysis of DSWI in cardiac surgery patients
Implementing an intravenous insulin protocol in your practice 351with diabetes in the preintravenous insulin infusion era pre- Thus, continuous intravenous insulin therapy for cardiacsented in this issue of Seminars by Brown and coworkers (See surgery patients not only saves lives, prevents infections, andBrown, et al, pp. 280-288) shows that the actual incidence of shortens hospital stays . . . , it also saves the hospital, and theDSWI in the population treated with subcutaneous sliding- health care system, money in the process.scale regular insulin given before meals and at bedtime is Krinsley performed a similar ﬁnancial analysis on medical5.6%.1 ICU patients. He compared the cost of care for 800 patients Moving from that historical “standard of care” to the cur- that received intensive glycemic management to 800 histor-rent “new” standard of care with three full days of tight gly- ical control patients treated at Stamford Hospital, a universi-cemic control with intravenous insulin thus results in an ty-afﬁliated community teaching hospital.23 The followingabsolute reduction in DSWI of 5.3%. A 5.3% reduction trans- costs were included: length of stay in the intensive care unit,lates into one DSWI saved for every 19 patients so treated. length of hospital stay outside of the ICU, ventilator days,Amortizing the incremental hospital costs of a single DSWI laboratory, pharmacy, diagnostic imaging, and the cost ofinto these 19 patients ($24,600/19) reveals that, in terms of glucose management. The cost savings with intensive glyce-saved DSWI costs, the hospital saves $1294 per patient, just mic management amounted to $1580 per patient. This isin terms of DSWI savings. likely an underestimation of the true savings, because it did In addition, recent data from Lazar show that cardiac sur- not include the cost savings associated with decreased inci-gery patients treated with subcutaneous sliding-scale regi- dence of renal dysfunction with subsequent decrease in themens of regular insulin given hourly level off at a postopera- need for dialysis, or the reduction in transfusion require-tive blood glucose of 267 mg/dL.25 In contrast, in a similar ments in those patients that received intensive glycemic man-patient population treated with the Portland Protocol at- agement. Of note, there was no increase in stafﬁng associatedtained a composite 3-day blood glucose of 122 mg/dL (See with the intensive glycemic management.Furnary & Wu, pp. 302-308). This represents a 145 mg/dL Van den Berghe and coworkers did a post-hoc health carereduction that can be achieved with a full 3-day implemen- resource utilization analysis of their randomized controlledtation of a continuous intravenous insulin regimen. It was trial in mechanically ventilated patients admitted to a surgicalfurther shown by the Portland group that length of stay is intensive care unit using insulin to normalize blood glucosereduced by 1 day for every 64 mg/dL reduction in 3-BG. to 80 to 110 mg/dL.24 The following costs were included:Therefore, conversion from sliding-scale SQ regular insulin ICU days, days of mechanical ventilation, days of hemodial-therapy to 3 days of continuous insulin therapy could be ysis/hemoﬁltration, vasopressors, inotropes, and antibiotics,expected to save an average of 2.27 LOS days for every car- blood transfusions, insulin administration, and blood glu-diac surgery patient (145 mg Ϭ dL/64 mg/dL/day) so treated. cose monitoring. Total health care costs were determined by The average hospital cost (including nursing, room, and multiplying the frequency of use of each resource by eachboard) of a nonoperating room day for a surgical patient is patient by its cost. Costs were presented as the median and$1537.a Thus, conversion from standard SQ sliding-scale in- interquartile range. The cost savings associated with strictsulin therapy to 3 days of continuous insulin therapy could normalization of blood glucose was 2638 Euros (equivalentbe expected to save $3482 (2.27 ϫ $1537) in direct hospital to USD $3476 as of March 10, 2007) per patient. These costlength of stay costs per patient. savings were due to reductions in ICU length of stay and Therefore, if a hospital chooses to implement 3 days of reduced morbidity such as renal failure, sepsis, blood trans-continuous insulin therapy for all cardiac surgery patients, it fusion, and mechanical ventilation dependency.would spend $138/patient for that therapy; in return, on a per It must be appreciated that all types of cost analysis arepatient basis it would save $1294 in prevented DSWI and based on assumptions that may not be accurate for all popu-$3482 in LOS savings for a total savings of $4776 ($1294 ϩ lations. However, most of the assumptions from the Portland$3482). Thus the Portland Protocol provides a NET SAV- experience used conservative assumptions. All of these anal-INGS to the hospital of $4638 (4776 Ϫ 138) for each cardiac yses are based on single studies which need to be conﬁrmedsurgery patient so treated with a full 3 days with intravenous by others. Still, the general agreement of all of the analysesinsulin therapy as compared with subcutaneous insulin ther- noted above makes a strong case for cost effectiveness of thisapy. therapy.aAverage of four published estimates of LOS costs to hospital for nursing Conclusion staff, room, and board is as follows: 1. Federal register; Ofﬁce of Man- Although there are several pitfalls to implementing an aggres- agement and Budget. Cost of hospital and medical care furnished by the United States. www.whitehouse.gov/omb/fedreg/tortﬁnal.pdf, page 20, sive insulin infusion protocol in clinical practice, concerns external nursing room and board costs $1773; 2. Governmental intra- can be avoided by setting achievable goals, educating staff agency costs ϭ $1635; 3. Maryland Department of Health. http://www. and administration to the clinical and economic beneﬁts of dhmh.state.md.us/publ-rel/html/pr041002a.htm; cost per Equivalent aggressive glycemic control, and moving out slowly to gain Inpatient Days in Maryland, $1473 in FY 2001; 4. Taheri PA, Butz DA, staff acceptance and ensure patient safety. Education needs to Greenﬁeld LJ: Length of stay has minimal impact on the cost of hospital admission. J Am Coll Surg 191:123-130, 2000; Average LOS day cost be the primary focus due to the poor understanding of dia- without major surgery ϭ $1326; average of these four references ϭ betes in general, and insulin in particular, by so many health $1537.25. care providers. Additional drawbacks and barriers may be
352 J.L. Kelly, I.B. Hirsch and A.P. Furnaryuncovered during implementation, and thus, ﬂexibility cou- 8. Malmberg K, Ryden L, Efendic S, et al: Randomized trial of insulin-pled with persistence will be necessary for the successful glucose infusion followed by subcutaneous insulin treatment in dia- betic patients with acute myocardial infarction (DIGAMI study); effectsimplementation. Having a physician, nurse, and pharmacist on mortality at 1 year. J Am Coll Cardiol 26:57-65, 1995champion works well in many institutions as when these 9. Van den Berghe G, Wouters P, Weekers F, et al: Intensive insulinchallenges occur each member can work with their peer. The therapy in critically ill patients. N Engl J Med 345:1359-1367, 2001beneﬁts of glycemic control are incremental, and even a mod- 10. Furnary AP, Wu YX, et al: Eliminating the diabetic disadvantage: theest improvement provides value to patients and the health Portland diabetic project. Sem Thorac Card Surg 18:301-307, 2006care system. 11. Vanhorebeek I, Ingels C, Van den Berghe G: Intensive insulin therapy in high-risk cardiac surgery patients: evidence from the Leuven ran- Finally, it must be emphasized that meticulous control of domized study. Sem Thorac Card Surg 18:308-315, 2006hyperglycemia resulting in improved outcomes, particularly 12. Garber AJ, Moghissi ES, Bransome ED, et al: American College of En-for critically ill patients, is no longer a hypothetical idea docrinology position statement on inpatient diabetes and metabolicchampioned by a few academic endocrinologists. Data to control. Endocr Pract 10:4-9, 2004 (suppl 2)date from scientists and clinicians from many areas of medi- 13. American Diabetes Association: Standards of medical care in diabetes.cine have conclusively proven the lifesaving and morbidity- Diabetes Care 28:S4-S34, 2005 (suppl 2) 14. Goldberg PA, Siegel MD, Sherwin RS, et al: Implementation of a safereducing beneﬁts of improved glycemia. For many popula- and effective insulin infusion protocol in a medical intensive care unit.tions, and particularly for cardiac surgery patients, this Diabetes Care 27:461-467, 2004improved care is not just cost-effective, but cost saving. It is 15. Ku SY, Sayre CA, Hirsch IB, et al: New insulin infusion protocol im-now our collective responsibility to translate these ﬁndings to proves blood glucose control in hospitalized patients without increas-all who can beneﬁt. Anything short of that would be unac- ing hypoglycemia. Jt Comm J Qual Saf 31:141-147, 2005ceptable. 16. Markovitz LJ, Wiechmann RJ, Harris N, et al: Description and evalua- tion of a glycemic management protocol for patients with diabetes undergoing heart surgery. Endocr Pract 8:10-18, 2002References 17. Krinsley JS: Effect of an intensive glucose management protocol on the 1. Brown JR, Edwards FH, O’Connor GT, et al: The Diabetic Disadvan- mortality of critically ill adult patients. Mayo Clin Proc 79:992-1000, tage: Historical outcomes measures in diabetic patients undergoing 2004 cardiac surgery- the pre-intravenous insulin era. Sem Thorac Card Surg 18. Brvar M, Mozina M, Bunc M: Prolonged hypoglycemia alter insulin 18:280-287, 2006 lispro overdose. Eur J Emerg Med 12:234-235, 2005 2. Capes S, Hunt D, Malmberg K, et al: Stress hyperglycemia and in- 19. Tofade, TS, Liles EA: Intentional overdose with insulin glargine and creased risk of death after myocardial infarction in patients with and insulin aspart. Pharmacotherapy 24:1412-1418, 2004 without diabetes: a systematic overview. Lancet 355:773-778, 2000 20. Bubder C, Lauritzen T, Faber O, et al: Insulin pharmacokinetics. Dia- 3. Bolk J, van der Ploeg T, Cornel JH, et al: Impaired glucose metabolism betes Care 7:188-199, 1984 predicts mortality after a myocardial infarction. Int J Cardiol 79:201- 21. Hirsch IB: Insulin analogues. N Engl J Med 352:174-183, 2005 214, 2001 4. Umpierrez GE, Isaacs SD, Bazargan N, et al: Hyperglycemia: an inde- 22. Furnary AP, Wu Y, Bookin SO: Effect of hyperglycemia and continuous pendent marker of inhospital mortality in patients with undiagnosed intravenous insulin infusions on outcomes of cardiac surgical proce- diabetes. J Clin Endocrinol Metab 87:978-982, 2002 dures: the Portland Diabetic Project. Endocr Pract 10:21-33, 2004 5. Furnary A, Zerr K, Grunkemeier G, et al: Continuous intravenous in- (suppl 2) sulin infusion reduces the incidence of deep sternal wound infection in 23. Krinsley JS: Cost analysis of intensive glycemic control in critically ill diabetic patients after cardiac surgical procedures. Ann Thorac Surg adult patients. Chest 129:644-650, 2006 67:352-362, 1999 24. Van den Berghe G, Wouters PJ, Kesteloot K, et al: Analysis of healthcare 6. Furnary AP, Gao G, Grunkemeier GL, et al: Continuous insulin infu- resource utilization with intensive insulin therapy in critically ill pa- sion reduces mortality in patients with diabetes undergoing coronary tients. Crit Care Med 34:612-616, 2006 artery bypass grafting. J Thorac Cardiovasc Surg 125:1007-1021, 2003 25. Lazar HL, Chipkin SR, Fitzgerald CA, et al: Tight glycemic control in 7. Capes S, Hunt D, Malmberg K, et al: Stress hyperglycemia and prog- diabetic coronary artery bypass graft patients improves perioperative nosis of stroke in nondiabetic and diabetic patients: a systematic over- outcomes and decreases recurrent ischemic events. Circulation 109: view. Stroke 32:2426-2432, 2001 1497-1502, 2004
Implementing an intravenous insulin protocol in your practice 353Appendix 1: Portland Continuous Insulin Infusion ProtocolVersion 2007.1 Page 1 of 3 Portland Continuous Intravenous Insulin Protocol ICU TARGET BLOOD GLUCOSE 80 to 120mg/dl Version 2007.1: ICU PHASE 3 1. Start “Portland Protocol” on all ICU patients as indicated below (place these orders on all ICU admission and postoperative order sets): • Initial BG check on admission & q 2hours X 2 • Hgb A1c if not done on admission to hospital. • Start Portland Protocol for any BG >125 mg/dl, including “non-diabetic” patients 2. Mix 1 unit Regular Human Insulin per 1 ml 0.9% Normal Saline, and start IV infusion via pump as follows: Blood Glucose IV Regular Insulin Initial Regular Insulin Rate: Syringe Bolus Units/Hour NIDDM or non-DM IDDM 110 to 124 mg/dl 0 None None 125 to 150 mg/dl 2 -- For DM patients only * 1 Unit / Hour 2 Units / Hour 151 to 180 mg/dl 4 Units 2 Units / Hour 3.5 Units / Hour 181 to 240 mg/dl 6 Units 3.5 Units / Hour 5 Units / Hour 241 to 300 mg/dl 8 Units 5 Units / Hour 6.5 Units / Hour 301 to 360 mg/dl 12 Units 6.5 Units / Hour 8 Units / Hour Greater than 360 mg/dl 16 Units 8 Units / Hour 10 Units / Hour 3. General Orders for ALL patients on “Portland Protocol”: • All intermittent (noncontinuous) IV medications should be mixed in normal saline. i. Do NOT administer intermittent (noncontinuous) IV medications mixed in dextrose-containing solutions • Do NOT use any dextrose-containing IV solutions for maintenance IV or daily IV fluids except when TPN is required. • If daily steroids are required: administer as a continuous infusion over a 24-hour period. i. Do NOT administer Bolus IV steroids or oral steroids while on IV insulin protocol. 4. Protocol Duration: • All Diabetic patients, and non-DM patients who remain hyperglycemic: Continue Protocol throughout ICU stay • Non-DM, euglycemic patients may stop protocol when target range maintained with <0.3 units / hour; then check BG every 2 hours X 6; then AC, 2 hours PC, and HS X 24 hours; if all BG < 125 may cease monitoring; if any BG > 125 resume Protocol. • Non-Diabetic Patients If continuing need for insulin exists on transfer after POD #3, and admission HgbA1c is greater than 6, ask physician to consult endocrinologist for DM workup and further follow-up orders. 5. ICU Transfer: Transition to Floor (ward) version of Portland Protocol on transfer out of ICU in: • All hyperglycemic patients: within 3 days of operation or ICU admission, or those eating less than 50% of a regular diet. • Non-Diabetic Patients If continuing need for insulin exists on transfer after POD #3, and admission HgbA1c is greater than 6, ask physician to consult endocrinologist for DM workup and further follow-up orders. 6. Protocol Cessation permissible ONLY on transfer in: • Diabetic patients if more than 3 days since last operation or ICU admission and eating more than 50% of a regular diet then: i. Restart pre-admission gylcemic control meds at 7 AM on day of transfer (OR ) Begin new Basal-Pranial SQ insulin therapy at 7AM on day of transfer ii. Then stop intravenous insulin infusion at 9AM prior to transfer iii. Continue to monitor BG – AC; 2 hours PC; and HS throughout rest of hospital stay • Non-Diabetic Euglycemic Patients may stop protocol If meet criteria outlined in #4 “Duration” • Non- Diabetic patients who remain hyperglycemic beyond the 3rd postoperative day -- no need to continue Protocol on transfer. However Endocrinology consultation should be requested by physician (see #5 above) 4. Test Blood Glucose (BG) by finger stick, arterial, or venous line drop samples. Frequency of BG testing is as follows: • Check BG every 30 minutes when: BG greater than 150mg/dl; or less than 80mg/dl; or after drip is stopped or decreased more than 50%; or after Bolus IV Insulin dose is given; or when rapidly titrating Vasopressors . • Check BG every Hour when BG is 80 – 150 mg/dl • Check BG every 2 Hours when BG is 80 - 120, with less than 15mg/dl BG variation over 4 hours and Insulin Rate remains unchanged for 4 hours – “Stable Infusion Rate”. Note – If any change in BG more than 15mg/dl, or any change in Insulin Rate more than 0.5 units: Return to checking BG every Hour. • During initiation of, rate change of, or cessation of any renal correction therapy or nutritional support Check BG every 30 minutes X 4 i. Renal correction therapy = Renal Dialysis, CVVH, CVVHD, Peritoneal dialysis, etc. ii. Nutritional support (enteral or parenteral) includes Tube Feedings, TPN, PPN 5. See Page 2 For Intravenous Insulin Titration Guidelines 6. See Page 3 For Meal Orders and adjunctive Periprandial SQ dosing schedules
354 J.L. Kelly, I.B. Hirsch and A.P. FurnaryAppendix 1 Continued Page 2 of 3 Portland Continuous Intravenous Insulin Protocol ICU TARGET BLOOD GLUCOSE 80 to 120mg/dl Version 2007.1: ICU PHASE 3 ICU: May titrate Insulin Infusion between 0-30 units /hour using the following as GUIDELINES to rapidly (within 3 hrs) achieve and maintain BG in target range (80-120). Round insulin Infusion to the nearest tenth of a unit (0.1) when necessary. Blood Action: Note: If BG less than 40mg/dl or greater than 450mg/dl, obtain confirmatory laboratory BG Glucose (BG) Less Than 50 Stop Insulin: • If not alert or if NPO: give 15 ml of D50W IV; If < 40 give 25 ml of D50W IV • If alert and taking PO give 8 ounces of juice PO OR 6 glucose tablets PO • Recheck BG every 30 minutes until greater than 80mg/dl • If next BG is < 50mg/dl: Double amount of previous treatment; If next BG is 50 – 65 mg/dl repeat treatment • When BG greater than 90mg/dl: Restart Insulin rate at 50% of previous rate & recheck BG in 30 minutes 50 to 64 Stop Insulin: • If Previous BG greater than 105mg/dl OR if symptomatic from hypoglycemia: º If NPO: give 15 ml of D50W IV; <OR> IF taking PO: give 4-6 ounces of juice OR 3 glucose tablets PO. • Recheck BG every 30 minutes until greater than 80mg/dl • If BG remains < 65 mg/dl : Repeat previous treatment • When BG greater than 90mg/dl: Restart Insulin rate at 50% of previous rate & recheck BG in 30 minutes 65 to 79 • If greater than last test: Decrease rate by 0.3 units / Hour • If lower than last BG by more than 40 mg/dl: Stop drip & recheck BG in 30 minutes (see bold * order) • If lower than last BG by 15 – 40 mg/dl: Decrease rate by HALF (50%) & recheck BG in 30 minutes • If equal to last BG or lower than last BG by less than 15mg/dl: Decrease rate by 0.5 Units / Hour *If infusion turned off, recheck BG in 30 min, when BG greater than 90mg/dl restart at 50% of previous rate & recheck BG in 30 minutes • Recheck BG every 30 minutes until greater than 80mg/dl 80 to 120 • If higher than last BG by more than 10mg/dl: Increase rate by 0.5 Units / Hour Target Range • If lower than last BG by more than 40 mg/dl: Stop drip & recheck BG in 30 minutes (see bold ** order) EXCELLENT! • If lower than last BG by 21–40 mg/dl: Decrease rate by HALF (50%) & recheck BG in 30 minutes May titrate • If lower than last BG by 10-20mg/dl: Decrease rate by 0.5 Units / Hour drip in ICU to ** If infusion turned off, recheck BG 30 min, if /when BG greater than 120mg/dl restart at 50% of previous rate maintain this • If within 10mg/dl of last BG same rate unless the following applies: range. See • FOR ANY BG in this range (even if within 10 mg/dl of last test) the following ALWAYS applies: Suggestions: º BG has consistently decreased each of last 4 measurements: Decrease rate by an additional 0.3 Units / Hour º BG has consistently increased each of last 4 measurements: Increase rate by an additional 0.2 Units / Hour 121 to 135 • If higher than last BG by more than 50mg/dl: Increase rate by 2 Units/Hour • If higher than last BG by 20 - 50mg/dl: Increase rate by 1 Unit / Hour • If higher than last BG by 0 - 20mg/dl: Increase rate by 0.5 Units / Hour • If lower than last BG by 1 - 20 mg/dl: Same rate • If lower than last BG by 21 - 40mg/dl: Decrease rate by 1 Unit / Hour • If lower than last BG by 41 – 60 mg/dl: Decrease rate by HALF (50%) and recheck BG in 30 minutes • If lower than last BG by more than 60 mg/dl: Stop drip & recheck BG in 30 minutes (see bold ** order below) **If infusion turned off, recheck BG 30 min, if /when BG greater than 125mg/dl restart at 50% of previous rate 136 to 150 • If higher than last BG by more than 30mg/dl: Increase rate by 2 Units/Hour & bolus with 4 units IV • If higher than last BG by 0 - 30mg/dl: Increase rate by 1 Unit / Hour & bolus with 2 units IV • If lower than last BG by 1 – 20: Increase rate by 1 Unit / Hour & bolus with 2 units IV • If lower than last BG by 21 to 50mg/dl: Same rate • If lower than last BG by 51 – 80mg/dl: Decrease rate by HALF (50%) and recheck BG in 30 minutes • If lower than last BG by more than 80mg/dl: Stop drip & recheck BG in 30 minutes (see bold ** order below) **If infusion turned off, recheck BG 30 min, if /when BG greater than 125mg/dl restart at 50% of previous rate 151 to 180 • If lower than last BG by more than 80mg/dl: Decrease rate by HALF (50%) • If lower than last BG by 30 –80mg/dl: Continue same rate • If lower than last BG by 0 – 30: Increase Insulin rate by 1 Unit / Hour & bolus with 2 units IV • If higher than last BG by 1- 20mg/dl: Increase Insulin rate by 2 Units / Hour & bolus with 4 units IV • If higher than last BG by more than 20mg/dl: Increase Insulin rate by 3 Units/Hour & bolus 6 units IV • Recheck BG in 30 minutes. Repeat BG every 30 minutes until less than 150mg/dl 181 to 240 • If lower than last BG by more than 100 mg/dl: Decrease rate by HALF (50%) • If lower than last BG by 50 – 100 mg/dl: Continue same rate • If lower than last BG by less than 50mg/dl OR higher than last BG: º BOLUS with 6 units Regular Insulin IV AND Increase Insulin rate by 2 Units / Hour • If BG remains greater than 180 mg/dl and has not decreased after 3 consecutive increases in Insulin: a. Give DOUBLE previous IV BOLUS dose up to a maximum of 20 units AND b. DOUBLE Insulin drip rate -- up to a maximum of 20 units / hour c. If on 20 units/hour and no response after 4 maximum boluses – CALL MD for further orders • Recheck BG in 30 minutes. Repeat BG every 30 minutes until less than 150mg/dl Greater than • If lower than last BG by more than 150 mg/dl: Decrease rate by HALF (50%) 240 • If lower than last BG by 101-150mg/dl : Same rate • If lower than last BG by 0- 100mg/dl OR if higher than last BG: º BOLUS with 10 Units Regular Insulin IV AND DOUBLE Insulin rate up to a maximum of 30 units / hour • If BG remains greater than 240 mg/dl and has not decreased after 3 consecutive increases in Insulin: d. Give DOUBLE previous IV BOLUS dose up to a maximum of 30 units AND e. DOUBLE Insulin drip rate -- up to a maximum of 30 units / hour f. If on 30 units/hour and no response after 4 maximum boluses – CALL MD for further orders • Recheck BG in 30 minutes. Repeat BG every 30 minutes until less than 150mg/dl IF BG GREATER THAN 300 for 4 CONSECUTIVE READINGS: CALL MD FOR ADDITIONAL IV BOLUS ORDERS
Implementing an intravenous insulin protocol in your practice 355Appendix 1 Continued Page 3 of 3 Portland Continuous Intravenous Insulin Protocol ICU TARGET BLOOD GLUCOSE 80 to 120mg/dl Version 2007. 1: ICU PHASE 37. Diet: 1800 ADA Diabetic Diet starts with any PO intake. When need to advance diet exists, may begin with FULL liquids or SUGAR-FREE clear liquids and advance as tolerated. Patient may take oral or enternal nutrition at any time in conjunction with this protocol.8. Prandial Subcutaneous Rapid-Acting Insulin Analogue (Humalog/Novolog/Apidra) Supplement in ADDITION to Insulin Infusion at MEALTIMES: a. For the patient’s FIRST meal give S.Q. Humalog/Novolog/Apidra immediately post-meal according to the following dosing schedule: Insulin Infusion Drip Eats Greater Eats 25% to Snacks or ROW # Rate at Than 50% of Meal less than First Meal 50% of Meal 25% of meal 0 to 1.9 Units / Hour 4 Units 2 Units 1 Unit 1 2 to 3.9 Units / Hour 6 Units 3 Units 2 Units 2 4 to 5.9 Units / Hour 8 Units 4 Units 3 Units 3 6 to 7.9 Units / Hour 10 Units 5 Units 4 Units 4 8 to 10 Units / Hour 12 Units 6 Units 5 Units 5 Over 10 Units / Hour 14 Units 7 Units 6 Units 6 b. Chart the ROW # used from the above dosing schedule from the initial meal = “Initial Row #”. c. Continue Protocol BG frequency monitoring and treatment as noted in the IV portion of this protocol. d. For all subsequent meals & periprandial S.Q. Insulin Analogue doses and titration use the table below. • Note: Ignore the insulin IV insulin infusion rate after the first periprandial dose calculation and adjust all further doses using row # references. • If consistently eating entire meal tray, give S.Q. Humalog/Novolog/Apidra when tray arrives at bedside. • If uncertain of oral intake, then give S.Q. Humalog/Novolog/Apidra immediately post-meal e. Based upon a postprandial BG reading obtained approximately 2 hours After Subcutaneous Analogue insulin was given, and using the “Initial Row #” as THE FIRST baseline row, titrate (adjust) the S.Q. dosing schedule Row # for the NEXT meal as follows: • If the 2 hour postprandial BG is greater than 175mg/dl, increase insulin schedule for next meal by TWO ROWS • If the 2 hour postprandial BG is 125 - 175mg/dl, increase insulin schedule for next meal by ONE ROW • If the 2 hour postprandial BG is 81 – 124mg/dl, then repeat this dosing schedule with next meal • If the 2 hour postprandial BG is 60 - 80mg/dl, then DECREASE insulin schedule for next meal by ONE ROW • If the 2 hour postprandial BG is less than 60mg/dl, then DECREASE insulin schedule for next meal by TWO ROWS ROW # Eats Greater Eats 25% to Snacks or Than 50% of Meal less than 50% of Meal 25% of meal 1 4 Units 2 Units 1 Unit 2 6 Units 3 Units 2 Units 3 8 Units 4 Units 3 Units 4 10 Units 5 Units 4 Units 5 12 Units 6 Units 5 Units 6 14 Units 7 Units 6 Units 7 16 Units 8 Units 7 Units 8 18 Units 9 Units 8 Units 9 20 Units 10 Units 9 Units 10 22 Units 11 Units 10 Units f. With each meal chart the ACTUAL ROW # used for S.Q. periprandial dosing. g. This previous meal ROW# becomes the new Baseline row # from which the NEXT meal-related periprandial dose of S.Q Analogue will again be adjusted according to the titration schedule in 8.e as read from the table above. h. Continue to titrate each subsequent meal-related S.Q. dose of Humalog/Novolog/Apidra according to the titration schedule in 8.e using the Row # actually used from the previous (Immediately preceding) meal as the baseline Row #.
356 J.L. Kelly, I.B. Hirsch and A.P. FurnaryAppendix 2: Yale Insulin Infusion Protocol(Reprinted with permission from Goldberg PA, Siegel MD, Sjerwom RS, et al: Implementation of a safe and effective insulininfusion protocol in a medical intensive care unit. Diabetes Care 27:461-467, 2004.)
Implementing an intravenous insulin protocol in your practice 357Appendix 3: UWMC Insulin Infusion Protocol
358 J.L. Kelly, I.B. Hirsch and A.P. FurnaryAppendix 3 Continued(Reprinted with permission from Trence DL, Kelly JL, Hirsch IB: The rationale and management of hyperglycemia for in-patientswith cardiovascular disease: time for change. J Clin Endocrinol Metab 88:2430-2437, 2003.)