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mplementing an Intravenous Insulin Protocol in Yourractice: Practical Advice to Overcome Clinical,dministrative, and Financial Barriers

anet L. Kelly, PharmD, BC-ADM, Irl B. Hirsch, MD, and Anthony P. Furnary, MD

Diabetes mellitus is the fourth most common comorbid condition among hospitalizedpatients, and 30% of patients undergoing open-heart surgery have diabetes. The linkbetween hyperglycemia and poor outcome has been well described, and large clinical trialshave shown that aggressive control of blood glucose with an insulin infusion can improvethese outcomes. The barriers to implementing an insulin infusion protocol are numerous,despite the fact that doing so is paramount to clinical success. Barriers include safetyconcerns, such as fear of hypoglycemia, insufficient nursing staff to patient ratios, lack ofadministrative and physician support, various system and procedural issues, and resis-tance to change. Key steps to overcome the barriers include building support with multi-disciplinary champions, involving key staff, educating staff, and administrators of theclinical and economic benefits of improving glycemic control, setting realistic goals,selecting a validated insulin infusion protocol, and internally marketing the success of theprotocol.Semin Thorac Cardiovasc Surg 18:346-358 © 2006 Elsevier Inc. All rights reserved.

KEYWORDS diabetes, insulin, hypoglycemia, hyperglycemia, economics

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iabetes mellitus is the fourth most common comorbidcondition among hospitalized patients, and 30% of pa-

ients undergoing open-heart surgery have diabetes.1 (Seerown, et al, pp. 281-288.) The link between hyperglycemiand poor hospital outcome has been well described,2-7 andarge well-designed clinical trials have shown that aggressiveontrol of blood glucose can improve these outcomes.8,9 Inhis issue of Seminars in Thoracic and Cardiovascular Surgerypdates of landmark studies from Furnary and Van denerghe both reveal that aggressive control of perioperativelood glucose independently reduces mortality by 60% inatients undergoing coronary artery bypass graftCABG).10,11 (See Furnary & Wu, pp. 302-308 and Van-orebeek, et al, pp. 309-316.)There is thus ample evidence in the literature that supports

he clinical importance of preventing hyperglycemia. How-

niversity of Washington Medical Center, School of Pharmacy, Division ofMetabolism, Endocrinology, and Nutrition, University of Washington,Seattle, WA; and Starr-Wood Cardiac Group, Providence St. VincentHospital, Portland, OR.

ddress reprint requests to Irl B. Hirsch, MD, University of Washington,Division of Metabolism, Endocrinology, and Nutrition, 1959 NE PacificStreet, Box 356176, Seattle, WA 98195. E-mail: ihirsch@u.washington.

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46 1043-0679/06/$-see front matter © 2006 Elsevier Inc. All rights reserved.doi:10.1053/j.semtcvs.2006.06.004

ver, the blood glucose threshold, at which increased mor-idity and mortality occur, differs for each of the outcomeeasures studied. Furthermore, the goal of euglycemia must

e mitigated by attention to the simultaneous prevention ofypoglycemia.The American College of Endocrinology (ACE) Consensus

tatement on inpatient diabetes management recommendshe following glycemic targets: blood glucose less than orqual to 110 mg/dL (6.1 mmol/L) for critical care patients,nd preprandial blood glucose of less than or equal to 110g/dL (6.1 mmol/L) with maximal blood glucose levels of no

reater than 180 mg/dL (10 mmol/L) for patients in noncrit-cal care units.12 The American Diabetes Association (ADA)upports these goals with slightly broader targets allowing forradual and safe implementation in the majority of hospitalettings. The ADA recommends blood glucose levels be kepts close to 110 mg/dL as possible and generally less than 180g/dL (10 mmol/L) for critical care patients. In noncritical

are units the ADA further recommends a preprandial bloodlucose target range of 90 to 130 mg/dL (5 to 7.2 mmol/L)nd maximal blood glucose less than 180 mg/dL (10 mmol/L)or patients in noncritical care units.13

To safely achieve these glycemic goals in clinical practice,

here must be firm supportive cross-collaboration among all

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Implementing an intravenous insulin protocol in your practice 347

edical professions caring for the patients and hospital ad-inistrative staff. Successful implementation of hospital-ide tight glycemic control will take the form of treatment

lgorithms, which advocates a stepwise approach toward eu-lycemic goals and appropriate blood glucose monitoring ofhese patients.

dentification of Barriershe barriers to implementing an insulin infusion protocoloth in the intensive care unit and on nonintensive careoors are numerous. In fact, implementation of an intrave-ous insulin protocol in the non-ICU setting may be partic-larly strewn with administrative, political, nursing, andedical challenges, despite the fact10 that doing so is para-ount to clinical outcomes success. (See Furnary & Wu, pp.

02-308.) Some of these are simply educational opportuni-ies, as barriers include safety concerns, such as fear of hypo-lycemia, insufficient nursing staff to patient ratios, lack ofdministrative and physician support, various system androcedural issues, and the subjective human resistance tohange.

Before implementing an intravenous infusion protocol, its imperative that current diabetes-related practices in thenstitution are evaluated and critical questions are addressed.

hat is the current level of glycemic control? Who is check-ng patients’ blood glucose? How frequently is it beinghecked? How supportive are medical staff and nursing ad-inistration for improving glycemic control? What educa-

ional mechanisms exist for disseminating published clinicalnformation to the nursing staff so that they fully understandhe clinical rationale for tight glycemic control? What are thexisting institutional rules and regulations regarding phar-acological intravenous infusions in the non-ICU setting?his will allow for identification of the unique barriers of the

nstitution.

trategies forvercoming Barriers

ey steps to overcome the barriers include building supportith multidisciplinary champions, involving key staff in therocess, educating staff and administrators of the benefits of

mproving glycemic control, and internally marketing thelinical success of the protocol. Additional caveats for successnclude starting with higher blood glucose targets, startingith a proven patient population (ICU or CCU), and using an

stablished insulin infusion protocol that has already beenalidated for safety and efficacy. Perhaps the most importantarrier-breaking strategy is repeated education of the medicalnd nursing staff. This empowers those in the trenches oflycemic control with the multitude of published clinicalata on the subject (such as those presented in this issue ofeminars). They thus learn that what they are doing is not justbout blood glucose control, but is actually about reducing

orbidity, mortality, and cost! S

ealistic Goalsne of the major pitfalls in implementing any protocol is to

et unrealistic glycemic goals. If the current baseline averagelood glucose for patients with diabetes is well over 200g/dL (11 mmol/L), then it is unrealistic to achieve the ACE/DA recommended goals as a first step. It would be a safernd more easily accepted strategy to implement a stepwisepproach, starting with an initial blood glucose goal of lesshan 200 mg/dL, and then progressively stepping down theoal as experience and comfort are gained. The Portland Pro-ocol is one that has been specifically designed with thistepwise implementation process in mind. This widely usedrotocol is available at five different target blood glucoseanges with separate protocols at each target range availableor both the ICU and the non-ICU settings. These can bereely downloaded at www.portlandprotocol.org. The rec-mmended time to move to a lower target range is when theean blood glucose obtained for all patients on the currentarticular protocol crosses below the next upper target limit.or example when the mean blood glucose of all patients soreated is 175 mg/dL, then it is time to move from a targetange of 150 to 200 mg/dL to a target range of 125 to 175g/dL.In addition to the target blood glucose, one must consider

he patient population. It will be easier to convince colleaguesnd staff of the importance of implementing an insulin infu-ion protocol for a patient population such as cardiac sur-ery, post-myocardial infarction, or surgical intensive careecause the benefits have been clearly established in the lit-rature. Once you have success in your institution with theseopulations, it will make it easier to move out to other pop-lations as well. Another important factor to consider is the

ocations where insulin infusions can be safely used in thenstitution. Starting on units already familiar with the use ofnsulin infusion protocols will improve success and can besed to gather support for moving to other areas within the

nstitution.

election of an Insulin Infusion Protocoleveral insulin infusion protocols have been validated inractice and published in the literature.8,9,14-17 They range

rom the simple to the very complex, and the glycemic goalsor these protocols are equally variable depending on thestablished glycemic goals at the time they were developed.he ideal insulin infusion protocol is based not only on theurrent blood glucose, but also on the rate of change in bloodlucose and the insulin sensitivity of the patient. In addition,he protocol should be easy to implement and have clear andpecific directions for titration, blood glucose monitoring,nd treatment of hypoglycemia. Many institutions developheir own insulin infusion protocol, which requires expertise,ime, and validation of safety and efficacy.

Choosing a published insulin protocol that has alreadyeen validated allows for more rapid implementation, with-ut the need for IRB approval. Table 1 compares some of theey features of various published insulin infusion protocols.

ome of these protocols are quite complex and rely heavily

Table 1 Key Features of Published Insulin Infusion Protocols

Characteristics DIGAMI8 Van den Berghe9 Portland Protocol5,6 Krinsley Protocol14 Yale Protocol11 UWMC Protocol13

SCTVS page reference 326-329 309-316 302-308 317-325 Not included Not includedPatient population Acute MI Adult surgical Cardiac surgery Medical and non-

cardiac surgicalAdult medical Adults (excluding obstetrical)

Location of use CCU ICU ICU and non-ICU telemetry ICU ICU Throughout the hospitalTarget (Goal) Blood

Glucose (BG) range125–180 mg/dl 80–110 mg/dl 150–200 mg/dl (1992-1998)

125–175 mg/dl (1999-2000)100–150 mg/dl (2001-2003)80–120 mg/dl (CVICU 2004)70–110 mg/dl (CVICU 2005)

<140 mg/dl 100–139 mg/dl 80–180 mg/dl

Frequency of BGmonitoring

Hourly until stable intarget range thendecrease to every 2hours and lessfrequently during thenight.

Hourly until stable in targetrange, then decrease to every2 and eventually every 4hours.

Every 30–60 minutes initiallywith specific parameters todecrease to every 2 hoursonce patient is stable intarget range

Hourly Hourly until stable intarget range, thendecrease to every 2and eventually every 4hours.

Hourly until stable in targetrange, then decrease toevery 2 and eventuallyevery 4 hours.

Time to reach target BGrange

75% patients werewithin goal rangewithin 6 hours

Data not available 90% within Target range by 3hours

Data not available Mean of 10.1 � 4.6 hrs 3.5 � 0.3 hrs (critical care)3.9 � 0.5 hrs (non-criticalcare)

Glycemic control results Mean BG at 24 hrswas 170 � 53 mg/dl.

Mean AM fasting blood glucosewas 103 � 19 mg/dl.

Average composite 3-dayblood glucose (3-BG) was121 � 20 mg/dl for 2005.(ICU and Ward)

Mean BG was130 � 55 mg/dl.

52% of patients werestable in the goalrange, with 93%achieving a clinicallyacceptable glycemicrange (80–199 mg/dl).

Patients were hyperglycemic(BG>180 mg/dl) for 15%(critical care) and 18%(non-critical care) of thetime they were receivinginsulin infusion therapy.

Hypoglycemia definition& rate

Hypoglycemia (BG<55mg/dl) occurred in17.8% of patients.

Hypoglycemia (BG<40 mg/dl)occurred in 5.1% of patients.

Hypoglycemia (BG<60 mg/dl) occurred in 1.5% of allpatients

Hypoglycemia (BG<40mg/dl) occurred in1.88% of allpatients.

Hypoglycemia (BG<60mg/dl) occurred in23% of patients

Hypoglycemia (BG<40 mg/dl) Occurred in: 3.6% incritical care 4% in non-critical care

Outcome results Use of intensivemetabolic controlwith insulin-glucoseinfusion followed bysubcutaneousinsulin reducedmortality at 1 year.One life was savedfor every 9 patientstreated.

Reduced ICU and hospitalmortality by over 30%. Alsoreductions in length of ICUstay, ventilatory support,renal replacement therapy,sepsis, and critical careneuropathy.

Decrease in hospitalmortality by 65% andreduced the incidence ofdeep sternal wound by63%. Decrease in lengthof stay by 2.0 days

Hospital mortality wasreduced 29.3%

Clinical outcomes notevaluated

Clinical outcomes notevaluated

Insulin titration Done according toprotocol by bedsidenurses.

Done by a team of speciallytrained nurses withassistance of physician.

Done according to protocolby bedside nurses.

Done according toprotocol by bedsidenurses.

Done according toprotocol by bedsidenurses.

Done according to protocolby bedside nurses.

348J.L.Kelly,I.B.Hirsch

andA.P.Furnary

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n clinical judgment, while others are simpler and easier tomplement in clinical practice. Three protocols, which theuthors feel are sufficiently detailed to allow for implemen-ation in clinical practice with minimal physician involve-ent in titration decisions, are described in more detail be-

ow.The Portland Protocol is a very effective protocol that has

een used safely and effectively in a large number of open-eart surgery patients in both critical care and telemetry set-ings. This protocol has been in use since the early 1990s withgradual decrease in the target blood glucose range. When

nitially implemented in 1991 the target blood glucose was50 to 200 mg/dL (8.2 to 11 mmol/L). In 1999 the targetlood glucose was reduced to 125 to 175 mg/dL (6.9 to 9.6mol/L) and then again in 2001 to 100 to 150 mg/dL (5.5 to

.2 mmol/L). A current Portland Protocol (version 2007.1)or the ICU with a goal blood glucose range of 80 to 120

g/dL is reproduced in Appendix 1 (Portland Protocols at var-ous target ranges are freely available for download at www.ortlandprotocol.org).The Portland Protocol is usually started during the surgical

rocedure. The protocol may be started the day before sur-ery if the patient is hospitalized and is found to have a bloodlucose level greater than 180 mg/dL. The Portland Protocols maintained in all cardiovascular ICU patients throughoutheir stay in that unit. The Portland Protocol is then contin-ed at least until 7 AM of the third postoperative day inatients who have left the intensive care unit and have goneo the telemetry floor. The initial infusion rate is determinedy the patient’s initial blood glucose and whether the patientas Type 1 or Type 2 diabetes. For patients substantiallybove target range, insulin boluses are used in addition toncreased infusion rate. Blood glucose is monitored by fingertick method or arterial line samples every 30 to 60 minutesntil stable, after which the frequency of blood glucose test-

ng can be reduced. This is a very efficient protocol with 90%f patients reaching target range within 3 hours, largely dueo the use of IV bolus insulin concomitant with increases innfusion rates.

The Yale Protocol was developed for medical intensive careatients with a goal blood glucose range of 100 to 139 mg/dL5.5 to 7.6 mmol/L) (Appendix 2).14 The initial bolus andnfusion rate are determined by dividing the patient’s currentlood glucose (eg, 350 mg/dL) by 100, to give a bolus dosend rate of infusion (eg, 3.5 unit bolus with an infusion ratef 3.5 units per hour). Blood glucose is monitored hourlyntil the patient is stable within the goal blood glucose range.ubsequent insulin infusion rates are determined by the cur-ent blood glucose and the rate of change using multipleables. Using this protocol, the mean time to achieve targetlood glucose levels was 10.1 � 4.6 hours with nurse-to-atient ratios of 1:1 or 1:2.The University of Washington Medical Center (UWMC)

nsulin infusion protocol was developed for use in all adultatients, surgical and medical, but excluding obstetrical pa-ients, in both critical care and noncritical care settings (Ap-endix 3).15 It is a column-based protocol, which was

dapted from the protocol by Markovitz and coworkers.16 m

he protocol is divided into four columns based on insulinensitivity. The first column is for the most insulin-sensitiveatients, and the fourth column is for patients with the great-st insulin resistance. The majority of patients start with therst algorithm or column. Insulin-resistant patients, such ashose undergoing coronary artery bypass grafting, receiving aransplant, requiring glucocorticoids; or who receive greaterhan 80 units per day of insulin as outpatients, start withlgorithm 2. The insulin infusion rate is determined by theatient’s current blood glucose and varies hourly until theatient is stable in the target range. If blood glucose targetsre not achieved or if the blood glucose has not decreased byt least 60 mg/dL in the preceding hour, the patient is movedp to the next algorithm. Patients move down to a less ag-ressive algorithm only if they experience hypoglycemia, de-ned as a blood glucose level of less than 60 mg/dL (3.3mol/L), or have two subsequent hourly blood glucose levels

ess than 70 mg/dL (3.8 mmol/L).

ducation and Empowerment of Staffnother important pitfall to avoid is the lack of sufficient andontinual staff education. Staff must understand that they areot just “fixing” an elevated blood glucose level, but reducingorbidity, mortality, and cost. Without continual reminders

f this, staff may lose sight of the value of improving glycemicontrol. No insulin infusion protocol can be safely imple-ented without ensuring that staff is knowledgeable in how

o use it. The best educational approach is a varied one thatllows for different learning styles and different work sched-les and is repeated at frequent intervals to compensate fortaff turnover. At UWMC we use a four-pronged approach.

e started with diabetes education days, which are a combi-ation of didactic lectures and discussion sessions regardinghe theory, rationale, and practical management of patientsith diabetes. These sessions are done on a voluntary basis

way from direct patient care. Staff that completed these ses-ions then assist with the second prong, which are smalln-service case studies done for each shift on the nursingtations periodically. These case studies are also available inn interactive Powerpoint™ presentation for staff membershat are unable to attend an in-service session or want aeview. The third prong is the availability of diabetes special-sts that are available via pager for questions. The fourth andnal prong is a mandatory competency examination to en-ure that staff can safely care for a patient on the insulinnfusion protocol. Each institution will have unique educa-ional needs and thus the plan will differ, but education is aey component of a successful insulin infusion protocol.

ear of Hypoglycemianother potential pitfall with implementation of an aggres-ive insulin infusion protocol is the risk of hypoglycemia andossible morbidity associated with it. The best way to avoidhis is to mandate frequent blood glucose monitoring withinhe protocol itself, have a clear and specific definition ofypoglycemia, and have specific nursing orders for the treat-

ent of hypoglycemia. This allows the nurse to rapidly treat

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350 J.L. Kelly, I.B. Hirsch and A.P. Furnary

hypoglycemic event before any neurologic sequelae or mor-idity occurs. Of course mandating does not guarantee com-liance, and it is more important to make sure that it isractical for staff to monitor the blood glucose as prescribed.Many hospitals restrict intravenous insulin infusion use to

ritical care units, because they perceive them as dangerousnd requiring close patient monitoring. They falsely believehat intravenous infusions are more risky than subcutane-usly administered insulin, when in reality they are safer withppropriate monitoring. The onset of action of intravenousnsulin is a mere minutes with a duration of action of onlybout an hour. In contrast subcutaneous insulin has a muchlower onset, but its duration of effect can be prolonged andnpredictable in acutely ill patients. There are numerous re-orts in the literature of prolonged and severe hypoglycemiaith overdose of subcutaneous insulin, including the rapid-

cting analogues.18,19 Permanent neurologic sequelae associ-ted with hypoglycemia has been linked to repeated androtracted episodes of hypoglycemia, rather than a singlepisode, which is rapidly corrected. Subcutaneous (SC) in-ulin can have as much as a 35% variability within the sameatient, while intravenous insulin is extremely predictable.20

ue to the short pharmacokinetics and pharmacodynamicsf intravenous insulin, blood glucose has been shown to beafely titrated in a non-ICU setting.15 Adequate monitoringust be performed for patients receiving an intravenous in-

usion, yet ideal frequency is not known. Paradoxically, over-onitoring is a major concern with SC insulin due to the longharmacodynamics of SC insulin, resulting in “insulin stack-

ng.”21

Decisions that revolve around an institution’s choice oflucose monitoring equipment are also important. Are thereufficient glucometers available, and are they strategicallyocated to eliminate the need for staff to search for them whenhey need one? Is the blood glucose monitor easy to use? Doest provide rapid and reliable results? Do staff members knowow to use it? If someone other than the bedside nurse ishecking the blood glucose, are the results communicated intimely manner? Attention to all of these questions and ed-cating staff of the importance of following the prescribedrequency of blood glucose monitoring are important to en-ure compliance.

Another important consideration surrounds documenta-ion of glucose and insulin infusion data. Where will bloodlucose levels be documented? How, when, and where willnsulin infusion rates be recorded? Will blood glucose data beraphed? Streamlining this process will improve compliance,implify the evaluation the glucose trends, and contribute toimely therapeutic decisions. Ideally this data should beracked in a computerized system at the bedside that canisplay data in various ways depending on the user’s prefer-nce. However, in the absence of a bedside electronic medicalecord, organized metabolic data sheets should be used. Theortland group makes theirs available for download at port-

andprotocol.org. Having the blood glucose data available inhis manner will aid physicians in transitioning patients toubcutaneous insulin or other therapies when clinically indi-

ated. The complexity of each step of the implementation

rocess speaks to the importance of the slow and steadypproach.

The future of this concern and of glycemic control in gen-ral is quite exciting due to the introduction of real-timeontinuous glucose sensors for outpatient use in 2006. Clin-cal trials in the hospital are lacking, but the potential torovide near-normal glucose control with an extremely lowisk of hypoglycemia could revolutionize the management ofyperglycemia in the hospital.

inancial Impactn this day and age of rising awareness and concern aboutscalating hospital costs, one of the major pitfalls to imple-entation of an intravenous infusion protocol may be the

dditional financial cost of that therapy to the hospital itself.ospital and nursing administrators are less likely to widely

ccept clinically effective protocols that overutilize hospitalesources and nursing time without a financial return on thatnvestment. However, if financial as well as clinical benefitsan be shown, then all parties—patients, physicians, nurses,nd hospitals—will derive a benefit and the protocol will benthusiastically accepted. To date, three studies have exam-ned the cost-benefit ratio for improved glycemic control inhe hospital setting in financial terms.22-24 (See also Hilleman,p. 359-365.)During the course of the Portland Diabetic project the

n-hospital cost for subcutaneous insulin injections given ev-ry 4 hours was compared with those of continuous intrave-ous insulin therapy. In this analysis not only were the directosts of insulin, syringes, intravenous bags, tubing, and glu-ometer strips taken into account, but the all-important in-irect costs of nursing time and pharmacy time were evalu-ted as well. Indirect costs were assessed by directly timing ofll nursing and pharmacist components of both subcutane-us and intravenous therapies. In this manner detailed hos-ital cost information was obtained.It was determined that the overall direct and indirect costs

or 3 days of subcutaneous insulin therapy averaged $32 peratient. In comparison, cost of a full 3-day implementation ofhe Portland Protocol, with its frequent BG checks and infu-ion changes, cost the hospital $170 per patient. The ques-ion that then remains is “Does the financial benefit to theospital exceed the extra $138 spent per patient on 3 days ofV insulin therapy?” This question can be answered for bothhe hospital itself and the health care system as a whole.

In terms of hospital savings the Portland Protocol reducedoth the incidence of deep sternal wound infection (DSWI)nd the length of stay (See Furnary & Wu, pp. 302-308).omparison of the total hospital costs in that study revealed

hat the additional incremental cost of a hospital stay for aardiac surgery patient who contracted a DSWI on the samedmission following open heart surgery averaged $24,600ore than that of similar patients who did not get a DSWI.verall DSWI rates in that study have been reduced to the

urrent (2002 to 2005) rate of 0.3% with three full days of theortland Protocol.

The meta-analysis of DSWI in cardiac surgery patients

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Implementing an intravenous insulin protocol in your practice 351

ith diabetes in the preintravenous insulin infusion era pre-ented in this issue of Seminars by Brown and coworkers (Seerown, et al, pp. 280-288) shows that the actual incidence ofSWI in the population treated with subcutaneous sliding-

cale regular insulin given before meals and at bedtime is.6%.1

Moving from that historical “standard of care” to the cur-ent “new” standard of care with three full days of tight gly-emic control with intravenous insulin thus results in anbsolute reduction in DSWI of 5.3%. A 5.3% reduction trans-ates into one DSWI saved for every 19 patients so treated.mortizing the incremental hospital costs of a single DSWI

nto these 19 patients ($24,600/19) reveals that, in terms ofaved DSWI costs, the hospital saves $1294 per patient, justn terms of DSWI savings.

In addition, recent data from Lazar show that cardiac sur-ery patients treated with subcutaneous sliding-scale regi-ens of regular insulin given hourly level off at a postopera-

ive blood glucose of 267 mg/dL.25 In contrast, in a similaratient population treated with the Portland Protocol at-ained a composite 3-day blood glucose of 122 mg/dL (Seeurnary & Wu, pp. 302-308). This represents a 145 mg/dLeduction that can be achieved with a full 3-day implemen-ation of a continuous intravenous insulin regimen. It wasurther shown by the Portland group that length of stay iseduced by 1 day for every 64 mg/dL reduction in 3-BG.herefore, conversion from sliding-scale SQ regular insulin

herapy to 3 days of continuous insulin therapy could bexpected to save an average of 2.27 LOS days for every car-iac surgery patient (145 mg � dL/64 mg/dL/day) so treated.The average hospital cost (including nursing, room, and

oard) of a nonoperating room day for a surgical patient is1537.a Thus, conversion from standard SQ sliding-scale in-ulin therapy to 3 days of continuous insulin therapy coulde expected to save $3482 (2.27 � $1537) in direct hospital

ength of stay costs per patient.Therefore, if a hospital chooses to implement 3 days of

ontinuous insulin therapy for all cardiac surgery patients, itould spend $138/patient for that therapy; in return, on a peratient basis it would save $1294 in prevented DSWI and3482 in LOS savings for a total savings of $4776 ($1294 �3482). Thus the Portland Protocol provides a NET SAV-NGS to the hospital of $4638 (4776 � 138) for each cardiacurgery patient so treated with a full 3 days with intravenousnsulin therapy as compared with subcutaneous insulin ther-py.

Average of four published estimates of LOS costs to hospital for nursingstaff, room, and board is as follows: 1. Federal register; Office of Man-agement and Budget. Cost of hospital and medical care furnished by theUnited States. www.whitehouse.gov/omb/fedreg/tortfinal.pdf, page 20,external nursing room and board costs $1773; 2. Governmental intra-agency costs � $1635; 3. Maryland Department of Health. http://www.dhmh.state.md.us/publ-rel/html/pr041002a.htm; cost per EquivalentInpatient Days in Maryland, $1473 in FY 2001; 4. Taheri PA, Butz DA,Greenfield LJ: Length of stay has minimal impact on the cost of hospitaladmission. J Am Coll Surg 191:123-130, 2000; Average LOS day costwithout major surgery � $1326; average of these four references �

c$1537.25.

Thus, continuous intravenous insulin therapy for cardiacurgery patients not only saves lives, prevents infections, andhortens hospital stays . . . , it also saves the hospital, and theealth care system, money in the process.Krinsley performed a similar financial analysis on medical

CU patients. He compared the cost of care for 800 patientshat received intensive glycemic management to 800 histor-cal control patients treated at Stamford Hospital, a universi-y-affiliated community teaching hospital.23 The followingosts were included: length of stay in the intensive care unit,ength of hospital stay outside of the ICU, ventilator days,aboratory, pharmacy, diagnostic imaging, and the cost oflucose management. The cost savings with intensive glyce-ic management amounted to $1580 per patient. This is

ikely an underestimation of the true savings, because it didot include the cost savings associated with decreased inci-ence of renal dysfunction with subsequent decrease in theeed for dialysis, or the reduction in transfusion require-ents in those patients that received intensive glycemic man-

gement. Of note, there was no increase in staffing associatedith the intensive glycemic management.Van den Berghe and coworkers did a post-hoc health care

esource utilization analysis of their randomized controlledrial in mechanically ventilated patients admitted to a surgicalntensive care unit using insulin to normalize blood glucoseo 80 to 110 mg/dL.24 The following costs were included:CU days, days of mechanical ventilation, days of hemodial-sis/hemofiltration, vasopressors, inotropes, and antibiotics,lood transfusions, insulin administration, and blood glu-ose monitoring. Total health care costs were determined byultiplying the frequency of use of each resource by eachatient by its cost. Costs were presented as the median and

nterquartile range. The cost savings associated with strictormalization of blood glucose was 2638 Euros (equivalento USD $3476 as of March 10, 2007) per patient. These costavings were due to reductions in ICU length of stay andeduced morbidity such as renal failure, sepsis, blood trans-usion, and mechanical ventilation dependency.

It must be appreciated that all types of cost analysis areased on assumptions that may not be accurate for all popu-

ations. However, most of the assumptions from the Portlandxperience used conservative assumptions. All of these anal-ses are based on single studies which need to be confirmedy others. Still, the general agreement of all of the analysesoted above makes a strong case for cost effectiveness of thisherapy.

onclusionlthough there are several pitfalls to implementing an aggres-ive insulin infusion protocol in clinical practice, concernsan be avoided by setting achievable goals, educating staffnd administration to the clinical and economic benefits ofggressive glycemic control, and moving out slowly to gaintaff acceptance and ensure patient safety. Education needs toe the primary focus due to the poor understanding of dia-etes in general, and insulin in particular, by so many health

are providers. Additional drawbacks and barriers may be

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352 J.L. Kelly, I.B. Hirsch and A.P. Furnary

ncovered during implementation, and thus, flexibility cou-led with persistence will be necessary for the successful

mplementation. Having a physician, nurse, and pharmacisthampion works well in many institutions as when thesehallenges occur each member can work with their peer. Theenefits of glycemic control are incremental, and even a mod-st improvement provides value to patients and the healthare system.

Finally, it must be emphasized that meticulous control ofyperglycemia resulting in improved outcomes, particularlyor critically ill patients, is no longer a hypothetical ideahampioned by a few academic endocrinologists. Data toate from scientists and clinicians from many areas of medi-ine have conclusively proven the lifesaving and morbidity-educing benefits of improved glycemia. For many popula-ions, and particularly for cardiac surgery patients, thismproved care is not just cost-effective, but cost saving. It isow our collective responsibility to translate these findings toll who can benefit. Anything short of that would be unac-eptable.

eferences1. Brown JR, Edwards FH, O’Connor GT, et al: The Diabetic Disadvan-

tage: Historical outcomes measures in diabetic patients undergoingcardiac surgery- the pre-intravenous insulin era. Sem Thorac Card Surg18:280-287, 2006

2. Capes S, Hunt D, Malmberg K, et al: Stress hyperglycemia and in-creased risk of death after myocardial infarction in patients with andwithout diabetes: a systematic overview. Lancet 355:773-778, 2000

3. Bolk J, van der Ploeg T, Cornel JH, et al: Impaired glucose metabolismpredicts mortality after a myocardial infarction. Int J Cardiol 79:201-214, 2001

4. Umpierrez GE, Isaacs SD, Bazargan N, et al: Hyperglycemia: an inde-pendent marker of inhospital mortality in patients with undiagnoseddiabetes. J Clin Endocrinol Metab 87:978-982, 2002

5. Furnary A, Zerr K, Grunkemeier G, et al: Continuous intravenous in-sulin infusion reduces the incidence of deep sternal wound infection indiabetic patients after cardiac surgical procedures. Ann Thorac Surg67:352-362, 1999

6. Furnary AP, Gao G, Grunkemeier GL, et al: Continuous insulin infu-sion reduces mortality in patients with diabetes undergoing coronaryartery bypass grafting. J Thorac Cardiovasc Surg 125:1007-1021, 2003

7. Capes S, Hunt D, Malmberg K, et al: Stress hyperglycemia and prog-nosis of stroke in nondiabetic and diabetic patients: a systematic over-

view. Stroke 32:2426-2432, 2001

8. Malmberg K, Ryden L, Efendic S, et al: Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in dia-betic patients with acute myocardial infarction (DIGAMI study); effectson mortality at 1 year. J Am Coll Cardiol 26:57-65, 1995

9. Van den Berghe G, Wouters P, Weekers F, et al: Intensive insulintherapy in critically ill patients. N Engl J Med 345:1359-1367, 2001

0. Furnary AP, Wu YX, et al: Eliminating the diabetic disadvantage: thePortland diabetic project. Sem Thorac Card Surg 18:301-307, 2006

1. Vanhorebeek I, Ingels C, Van den Berghe G: Intensive insulin therapyin high-risk cardiac surgery patients: evidence from the Leuven ran-domized study. Sem Thorac Card Surg 18:308-315, 2006

2. Garber AJ, Moghissi ES, Bransome ED, et al: American College of En-docrinology position statement on inpatient diabetes and metaboliccontrol. Endocr Pract 10:4-9, 2004 (suppl 2)

3. American Diabetes Association: Standards of medical care in diabetes.Diabetes Care 28:S4-S34, 2005 (suppl 2)

4. Goldberg PA, Siegel MD, Sherwin RS, et al: Implementation of a safeand effective insulin infusion protocol in a medical intensive care unit.Diabetes Care 27:461-467, 2004

5. Ku SY, Sayre CA, Hirsch IB, et al: New insulin infusion protocol im-proves blood glucose control in hospitalized patients without increas-ing hypoglycemia. Jt Comm J Qual Saf 31:141-147, 2005

6. Markovitz LJ, Wiechmann RJ, Harris N, et al: Description and evalua-tion of a glycemic management protocol for patients with diabetesundergoing heart surgery. Endocr Pract 8:10-18, 2002

7. Krinsley JS: Effect of an intensive glucose management protocol on themortality of critically ill adult patients. Mayo Clin Proc 79:992-1000,2004

8. Brvar M, Mozina M, Bunc M: Prolonged hypoglycemia alter insulinlispro overdose. Eur J Emerg Med 12:234-235, 2005

9. Tofade, TS, Liles EA: Intentional overdose with insulin glargine andinsulin aspart. Pharmacotherapy 24:1412-1418, 2004

0. Bubder C, Lauritzen T, Faber O, et al: Insulin pharmacokinetics. Dia-betes Care 7:188-199, 1984

1. Hirsch IB: Insulin analogues. N Engl J Med 352:174-183, 20052. Furnary AP, Wu Y, Bookin SO: Effect of hyperglycemia and continuous

intravenous insulin infusions on outcomes of cardiac surgical proce-dures: the Portland Diabetic Project. Endocr Pract 10:21-33, 2004(suppl 2)

3. Krinsley JS: Cost analysis of intensive glycemic control in critically illadult patients. Chest 129:644-650, 2006

4. Van den Berghe G, Wouters PJ, Kesteloot K, et al: Analysis of healthcareresource utilization with intensive insulin therapy in critically ill pa-tients. Crit Care Med 34:612-616, 2006

5. Lazar HL, Chipkin SR, Fitzgerald CA, et al: Tight glycemic control indiabetic coronary artery bypass graft patients improves perioperativeoutcomes and decreases recurrent ischemic events. Circulation 109:

1497-1502, 2004

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Implementing an intravenous insulin protocol in your practice 353

ppendix 1: Portland Continuous Insulin Infusion Protocolersion 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

Syringe BolusInitial Regular Insulin Rate:

Units/HourNIDDM or non-DM IDDM

110 to 124 mg/dl 0 None None125 to 150 mg/dl 2 -- For DM patients only * 1 Unit / Hour 2 Units / Hour151 to 180 mg/dl 4 Units 2 Units / Hour 3.5 Units / Hour181 to 240 mg/dl 6 Units 3.5 Units / Hour 5 Units / Hour241 to 300 mg/dl 8 Units 5 Units / Hour 6.5 Units / Hour301 to 360 mg/dl 12 Units 6.5 Units / Hour 8 Units / HourGreater 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 transferii. 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 Ratemore 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 4i. 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

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354 J.L. Kelly, I.B. Hirsch and A.P. Furnary

ppendix 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 targetrange (80-120). Round insulin Infusion to the nearest tenth of a unit (0.1) when necessary.

BloodGlucose (BG)

Action: Note: If BG less than 40mg/dl or greater than 450mg/dl, obtain confirmatory laboratory 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 120Target RangeEXCELLENT!May titratedrip in ICU tomaintain thisrange. SeeSuggestions:

• If higher than last BG by more than 10mg/dl: Increase rate by 0.5 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 21–40 mg/dl: Decrease rate by HALF (50%) & recheck BG in 30 minutes• If lower than last BG by 10-20mg/dl: Decrease rate by 0.5 Units / Hour

** If infusion turned off, recheck BG 30 min, if /when BG greater than 120mg/dl restart at 50% of previous rate• If within 10mg/dl of last BG same rate unless the following applies:• FOR ANY BG in this range (even if within 10 mg/dl of last test) the following ALWAYS applies: 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 / Hour121 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 ANDb. DOUBLE Insulin drip rate -- up to a maximum of 20 units / hourc. 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/dlGreater than 240

• If lower than last BG by more than 150 mg/dl: Decrease rate by HALF (50%)• 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 ANDe. DOUBLE Insulin drip rate -- up to a maximum of 30 units / hourf. 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/dlIF BG GREATER THAN 300 for 4 CONSECUTIVE READINGS: CALL MD FOR ADDITIONAL IV BOLUS ORDERS

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Implementing an intravenous insulin protocol in your practice 355

ppendix 1 Continued Page 3 of 3 Portland Continuous Intravenous Insulin Protocol ICU TARGET BLOOD GLUCOSE 80 to 120mg/dl

Version 2007. 1: ICU PHASE 3

7. Diet: 1800 ADA Diabetic Diet starts with any PO intake. When need to advance diet exists, may begin with FULL liquids or SUGAR-FREEclear 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 atMEALTIMES:a. For the patient’s FIRST meal give S.Q. Humalog/Novolog/Apidra immediately post-meal according to the following dosing

schedule:

Insulin Infusion DripRate at

First Meal

Eats GreaterThan

50% of Meal

Eats 25% to50% of Meal

Snacks orless than25% of

meal

ROW #

0 to 1.9 Units / Hour 4 Units 2 Units 1 Unit 12 to 3.9 Units / Hour 6 Units 3 Units 2 Units 24 to 5.9 Units / Hour 8 Units 4 Units 3 Units 36 to 7.9 Units / Hour 10 Units 5 Units 4 Units 48 to 10 Units / Hour 12 Units 6 Units 5 Units 5Over 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 dosesusing 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, andusing the “Initial Row #” as THE FIRST baseline row, titrate (adjust) the S.Q. dosing schedule Row # for the NEXT meal asfollows:

• 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 GreaterThan

50% of Meal

Eats 25% to50% of Meal

Snacks orless than25% of

meal

1 4 Units 2 Units 1 Unit2 6 Units 3 Units 2 Units3 8 Units 4 Units 3 Units4 10 Units 5 Units 4 Units5 12 Units 6 Units 5 Units6 14 Units 7 Units 6 Units7 16 Units 8 Units 7 Units8 18 Units 9 Units 8 Units9 20 Units 10 Units 9 Units10 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 #.

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(i

356 J.L. Kelly, I.B. Hirsch and A.P. Furnary

ppendix 2: Yale Insulin Infusion Protocol

Reprinted with permission from Goldberg PA, Siegel MD, Sjerwom RS, et al: Implementation of a safe and effective insulinnfusion protocol in a medical intensive care unit. Diabetes Care 27:461-467, 2004.)

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Implementing an intravenous insulin protocol in your practice 357

ppendix 3: UWMC Insulin Infusion Protocol

A

(w

358 J.L. Kelly, I.B. Hirsch and A.P. Furnary

ppendix 3 Continued

Reprinted with permission from Trence DL, Kelly JL, Hirsch IB: The rationale and management of hyperglycemia for in-patients

ith cardiovascular disease: time for change. J Clin Endocrinol Metab 88:2430-2437, 2003.)