Postoperative Morbidity and Mortality in Type-2 Diabetics After Fast-Track Primary Total Hip and Knee Arthroplasty Christoffer C. Jørgensen, MD,*† Sten Madsbad MD, DMSci,‡ and Henrik Kehlet, MD, PhD,*† on behalf of the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Collaborative Group§ BACKGROUND: Diabetes is a risk factor for postoperative morbidity, which includes total hip and knee arthroplasty. However, no previous studies have been done in a fast-track setting with optimized perioperative care, including spinal anesthesia, multimodal opioid-sparing analgesia, early mobilization, and discharge to home, which improved postoperative outcome. METHODS: We performed an observational cohort study using prospective data in primary total hip and total knee arthroplasty with a standardized fast-track approach. Eight hundred ninety type 2 diabetics were successfully propensity matched with 7165 nondiabetics. Subanalyses on antihyperglycemic treatment were done using the Danish National Database of Reimbursed Prescriptions for information on dispensed prescriptions 6 months preoperatively. Length of hospital stay (LOS), 90-day readmissions, and mortality were found through the Danish National Health Registry and medical charts. Multiple logistic regression analyses on LOS > 4 days and readmissions were used to further adjust for demographics, comorbidity, and department of surgery. To further evaluate the clinical relevance of type 2 diabetes, we estimated the number of surgical type 2 diabetics needed for 1 more occurrence of LOS > 4 days or readmissions (adjusted number needed to harm [NNH]). RESULTS: Although more type 2 diabetics (11.3%) than nondiabetics (8.1%) had LOS > 4 days (unadjusted P = 0.001), there was no association between type 2 diabetes and LOS > 4 days when adjusting for covariates (odds ratio: 1.19 [0.93–1.54]; P = 0.172). Correspondingly, the NNH was 78 but ranged between 31 and infinity. Type 2 diabetes was not associated with 30(1.02 [0.75–1.39]; P = 0.897) or 90-day readmissions (1.22 [0.87–1.71]; P = 0.254), and with an NNH of 957 (59–∞) and 115 (35–∞), respectively. Insulin-treated type 2 diabetes was associated with increased risk of specific “diabetes-related” morbidity (1.95 [1.13–3.35]; P = 0.016). CONCLUSIONS: Type 2 diabetes per se has limited influence on postoperative morbidity in fasttrack total hip and knee arthroplasty. (Anesth Analg 2015;120:230–8)
T
he annual number of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) has been steadily increasing throughout the past decade, with a concomitant increase in number of comorbidities.1 One of the reasons for the increase in comorbidity is the increasing prevalence of diabetes,2 likely due to increased age and prevalence of obesity in the general population and increased lifespan among diabetics in most Western countries.3 Diabetes is a generally acknowledged risk factor for postoperative mortality and morbidity in many types of From the *Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark; †The Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement, Copenhagen, Denmark; and ‡Department of Endocrinology, Hvidovre University Hospital, Copenhagen University, Copenhagen, Denmark. §The members of the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Collaborative Group are coauthors of this study and are listed in the Appendix. Accepted for publication July 9, 2014. Funding: This work was sponsored by a grant (grant number R25-A2702) from the Lundbeck Foundation, Denmark. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Christoffer C. Jørgensen, MD, Section for Surgical Pathophysiology, Rigshospitalet, Blegdamsvej 9 2100, Copenhagen, Denmark. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000451
230 www.anesthesia-analgesia.org
surgeries.4,5 This also applies to major joint arthroplasty,6–8 although a few recent studies have been unable to demonstrate such association.9,10 Furthermore, pre- and perioperative hyperglycemia are independent predictors of postoperative morbidity after noncardiac surgery5 and specifically after major joint arthroplasty.6,11,12 This finding has led to suggestions of aggressive postoperative glycemic control,13 despite concerns about the increasing risk of hypoglycemia.14 Consequently, specific considerations regarding the perioperative continuum of care in the diabetic patient14,15 and increased focus on perioperative blood glucose management are recommended.16,17 No previous studies of THA and TKA in diabetics have been done in a standardized fast-track setting with optimized perioperative care, including spinal anesthesia, opioid-sparing multimodal analgesia, early mobilization, and discharge to home, which improved outcome after surgery.18 Because the fast-track approach has also been shown to reduce postoperative insulin resistance,19 there is a need to clarify the role of preoperative diabetes in fast-track surgery20 and to elucidate which types of postoperative morbidities occur in these potential high-risk patients.21 Using prospectively collected data, we investigated the association between diabetes and length of hospital stay (LOS) > 4 days, 30- and 90-day readmissions, and mortality in 8055 unselected patients undergoing primary elective unilateral THA and TKA with a standardized fast-track January 2015 • Volume 120 • Number 1
approach. We also studied whether there was an association between the intensity of antihyperglycemic treatment (insulin, oral antihyperglycemics, and diet treatment) and LOS > 4 days and readmissions. Finally, we estimated the number of surgical type 2 diabetics needed for 1 additional case of LOS > 4 days and readmissions (the adjusted number needed to harm [NNH]),22,23 thereby providing a more clinically oriented measure of the specific influence of diabetes on postoperative outcomes after fast-track THA and TKA.
METHODS
All data were collected from 7 departments between February 1, 2010, and November 30, 2012. No approval was needed from the Regional Ethics Committee because this was an analytic observational cohort study using existing prospectively collected data. Permission was acquired from the Danish Data Protection Agency and the Danish National Board of Health to review and store deidentified medical records without informed authorization of release of protected health information.
Preoperative Data
From February 1, 2010, all patients undergoing elective primary THA or TKA at hospitals participating in the Lundbeck Foundation Centre for Hip and Knee Replacement Collaboration have been completing a simple preoperative questionnaire on various patient characteristics. These include body mass index (BMI), living alone/with others, preoperative use of walking aids (yes/no), and known comorbidity such as type 1 and type 2 diabetes, pharmacologically treated cardiac disease, hypercholesterolemia, and hypertension. Staff is available for completing the questionnaire, and completeness of data is >95% of all procedures performed at the participating departments.24 Data are stored in the Lundbeck Foundation Centre database, which is registered as an ongoing study registry on preoperative risk factors on ClinicalTrials.gov (ID: NCT01515670). For this study, further information on specific pharmacologic antihyperglycemic treatment 6 months before surgery was acquired through the Danish National Database of Reimbursed Prescriptions, which registers all prescriptions with reimbursements dispensed at Danish pharmacies.25 In Denmark, all antihyperglycemic medications are reimbursed, and the use of prescription databases has been shown to have a positive predictive value of 98% for type 2 diabetics using oral antihyperglycemics.26 If patients reported type 2 diabetes but had no prescriptions in the Danish National Database of Reimbursed Prescriptions, they were considered as having “diet treatment.” Thirty-six patients didn’t report diabetes but had prescriptions on antihyperglycemic drugs and were thus classified as diabetics.
Perioperative Treatment
The participating departments all used a similar perioperative fast-track approach, including spinal anesthesia, opioid-sparing multimodal analgesia, minimal use of drains and catheters, mobilization on day of surgery, and functional discharge criteria.27 Median LOS of 2 to 3 days until discharge to home has been reported in a smaller cohort included in this study.24
January 2015 • Volume 120 • Number 1
Preoperative evaluation of diabetic status (HbA1C or fasting glucose) was at the discretion of the consulting anesthesiologist. Diabetic patients were typically scheduled for surgery early in the day and intraoperative use of 50 to 100 mL/h of IV glucose (5%)-insulin-potassium or glucose (5%)-insulin was standard in all departments. Intraoperative blood glucose was monitored each hour followed by appropriate adjustments of infusion rate of glucose and insulin. An intraoperative blood glucose >5 and 4 days was chosen as the cutoff for “prolonged” hospitalization because we have previously established that >80% of patients are discharged within 4 days, suggesting that patients with longer LOS have had complications.24 In case of transfer between hospitals/departments, LOS > 4 days, or 90-day readmissions, discharge forms and medical charts were consulted to determine primary reasons for these occurrences. Causes of in-hospital mortality were evaluated using the complete medical charts and autopsy reports if available. Causes of mortality outside hospital were evaluated using death certificates and/or autopsy reports if available. Finally, we constructed a composite outcome of “diabetes-related” morbidity, defined as the occurrence of specific postoperative morbidity more frequently occurring in diabetics than in nondiabetics4,6–8,29 or due to common diabetesinduced organ dysfunctions, and resulting in LOS > 4 days or readmissions. This included any case of cardiac arrhythmia, acute congestive heart failure, myocardial infarction, prosthetic or wound infections, renal insufficiency, cerebral attacks (transient ischemic attacks or cerebral stroke), pneumonia, and urinary tract infection causing LOS > 4 days or readmissions, as well as sepsis and dysregulated blood glucose causing LOS > 4 days and “other infections” causing readmission. All categories of outcome variables were predefined before data analysis (Table 1).
Study Outcomes
Our primary aim was to investigate the association of diabetes and LOS > 4 days, readmissions, and mortality within 90 days postoperatively, both overall and related to antihyperglycemic treatment regimens.
www.anesthesia-analgesia.org
231
Type-2 Diabetics and Fast-Track Hip and Knee Arthroplasty Table 1. Definitions of Complications Causes of LOS > 4 days Category Complications related to general or spinal anesthesia, postanesthetic Anesthetic cramps, difficulties with intubation, etc. complications Wound-related infections Prosthetic infections Hip displacements during admission Hip displacement Symptomatic DVT or PE DVT/PE Low hemoglobin leading to blood transfusion or continued observation Anemia Dizziness during mobilization with normal fluid balance and hemoglobin Dizziness/OI Surgically related pain and pain of other causes Pain (chronic pain patients, back pain, etc.) Falls Falls Side effects of pain treatment or other medication; prolonged Medication/ mobilization without further explanation mobilization Arterial thrombosis, fractures without trauma, intrasurgical Other surgical complications, prosthesis malfunction, bleeding sequelae episodes, swelling, and hematomas Arrhythmias, heart insufficiency, myocardial infarctions, low blood Cardiac pressure related to preoperative severe heart disease Pneumonia, chronic obstructive lung disease, dyspnea, atelectasis Pulmonary Ischemic stroke and other infarctions, transient cerebral ischemia, Cerebral delirium, preoperative neurologic, or psychiatric disease Ileus, dyspepsia, gastritis, gastric ulcers and other gastrointestinal Gastrointestinal bleeds, obstipation Renal insufficiency, dehydration, potassium or sodium Renal outside reference values Urinary retention, problems with urinary catheters, urinary tract Urologic infections Severe infection resulting in multiple organ affection and Sepsis described as a state of sepsis in discharge papers Sleep apnea, dysregulated blood glucoses, symptoms Other medical sequelae of addisonian crisis, dysregulated regular anticoagulant treatment Social reasons for continued admission, other elective Social/unrelated surgery during admission, preoperative hemophilia, causes unspecified symptoms with no diagnoses Standard discharge papers stating successful No morbidity surgery and rehabilitation Causes of 90-day readmissions Prosthetic infection treated with revision, wound incision, or IV antibiotics Hip displacements without falls Surgery due to unsatisfactory mobility of the knee Revision surgery due to prosthesis malfunction or suboptimal placement Description of prosthesis-related fracture without any preceding trauma Wound complications, hematoma, muscle rupture, other reoperations, arterial thrombosis DVT or PE confirmed by US, CT, or lung scintigraphy Symptoms of anemia followed by blood transfusion Pain in relation to recent surgery Falls mentioned as reason for admission regardless of injury Need of further rehabilitation, dizziness, nausea, and obstipation associated with opioid use Arrhythmias, myocardial infarction, heart insufficiency, and unverified acute coronary syndrome with no other apparent diagnosis Pneumonia, worsening of chronic obstructive lung disease,a dyspnea Transient cerebral ischemia, stroke, cerebral bleeds Ileus, gastric ulcers or gastritis, obstipation unrelated to opioid treatment, diarrhea Renal insufficiency Urinary tract infection,a urinary retention, hematuria Other types of infections, syncope,a unspecific indisposition DVT or PE not found and no other treatment prescribed Suspected, but unconfirmed infection and no antibiotic treatment prescribed
Category Prosthetic infections
Included as “diabetes-specific morbidity”
All cases
Only arrhythmias, heart insufficiency, and myocardial infarctions Only pneumonias Only strokes, infarctions, and transient cerebral ischemia
Only renal insufficiency and dehydration Only urinary tract infections All cases Only dysregulated blood glucoses
Included as “diabetes-specific morbidity” All cases
Hip displacement Knee manipulation Revision Fracture without trauma Other surgical sequelae DVT/PE Anemia Pain Falls Medication/mobilization Cardiac Pulmonary Cerebral Gastrointestinal Renal Urologic Other medical sequelae Unverified DVT/PE Unverified wound infection
Only arrhythmias, heart insufficiency, and myocardial infarctions Only pneumonia All cases
All cases Only urinary tract infection Only other types of infections
DVT = Deep venous thrombosis; PE = pulmonary embolism; US = ultrasound; CT = computer tomography; LOS = length of stay; OI = orthostatic intolerance. a Included for the first 30 days only.
232 www.anesthesia-analgesia.org
anesthesia & analgesia
Our second aim was to determine the relationship between preexisting diabetes and its treatment regimen and the occurrence of “diabetes-related morbidity” postoperatively, with an adjusted NNH22,23 for both LOS > 4 days, 30- and 90-day readmissions, and “diabetes-related comorbidity.” The adjusted NNH is the number of surgical type 2 diabetics needed for 1 more case of LOS > 4 days, readmission, or diabetes-related morbidity related specifically to the presence of diabetes while controlling for other confounders.22,23 During data preparation, we found that there were too few patients with type 1 diabetes to include them in the main analyses. Crude results for these few patients are therefore reported separately.
Statistics
Distribution of data was assessed using KolmogorovSmirnov with Lilliefors correction. Nonparametric data are reported as medians with interquartile ranges (IQR). MannWhitney U test was used for unadjusted analysis of nonparametric data, while χ2 test and Fisher exact test were used for categorical data when appropriate. To adjust for baseline differences between type 2 diabetics and nondiabetics, we calculated propensity scores30 using logistic regression with type 2 diabetes as outcome and age, sex, BMI, use of walking aids, operated joint, living alone/in institution/with others, pharmacologically treated cardiac disease, treated hypertension, and treated hypercholesterolemia as covariates. Age and BMI were entered as continuous covariates, while 2 separate variables were created regarding living alone or in institution using living with others as reference. The remaining variables were dichotomized (present/not present) with type 2 diabetes treatment categorized as insulin (with/without oral treatment), oral antihyperglycemic drugs only, and diet only (no pharmacologic treatment) versus nondiabetics for subanalyses. Of 8804 consecutive surgical patients, we initially excluded 36 (0.4%) due to missing information on diabetic status. Of the remaining 8768 procedures with completed preoperative questionnaires and information on diabetes, 43 (0.5%) procedures were in type 1 diabetics and 957 were in type 2 diabetics (10.9%). The percentage of type 2 diabetics was 9.3%–12.7% of all procedures in the different departments. It was possible to calculate propensity scores for 890 (93.0%) procedures in type 2 diabetics and for 7414 (95.4%) in nondiabetics. The C-statistic for the propensity model was 0.82, indicating a satisfactory predictive power. Trimming of the data set was performed to further improve accuracy of the model by excluding 249 procedures (3.0%) for which there was no propensity score overlap between groups.31 Thus, the final study population consisted of 890 (11.0%) procedures in type 2 diabetics and 7165 (89.0%) in nondiabetics. Analysis on outcomes was done using multiple logistic regressions, adjusting for patient characteristics and for propensity score as a continuous variable in a “doubly robust” model.30 Department of surgery (dichotomized into those with significantly more readmissions than the department with the fewest versus others) was also included in the multiple regression analysis to adjust for potential logistical and
January 2015 • Volume 120 • Number 1
population differences not otherwise accounted for in the standardized perioperative setup. Only the first readmission was included for regression analysis. We also tested for relevant interactions using pairwise separate models and applying the Wald test statistics. Results are reported as adjusted odds ratios (OR) with 95% confidence intervals (95% CI) and a 2-tailed P-value of 4 days (unadjusted P = 0.001; Fig. 1, A), there was no association between LOS > 4 days and type 2 diabetes when adjusting for covariates. This was regardless of antihyperglycemic treatment (Table 3). When comparing the causes of LOS > 4 days, renal, urologic, and cerebral complications were significantly more frequent in type 2 diabetics (Table 4). Readmissions within 30 and 90 days were both more frequent in type 2 diabetics (6.5% and 10.2%) than in nondiabetics (5.5% and 7.8%) (Fig. 1, B and C). However, after adjusting for covariates, no association between type 2 diabetes and 30- or 90-day readmissions was found (Table 3). Renal and urologic complications reoccurred more frequently in type 2 diabetics (Table 4). Finally, 90-day all-cause mortality was 0.3% in both type 2 diabetics (n = 3) and in nondiabetics (n = 23).
Secondary Outcomes, Diabetes-Related Morbidity, and Adjusted Number Needed to Harm
The composite outcome of diabetes-related morbidity occurred in 6.0% of type 2 diabetics and in 3.6% of nondiabetics. (Fig. 1, D). After covariate adjustment, only insulintreated type 2 diabetes was found to be associated with diabetes-related morbidity (Table 3). Because there was no significant association between type 2 diabetes and study outcomes, infinity was included in all estimates of the adjusted NNH (Table 3).
Type 1 Diabetics
In the 43 excluded type 1 diabetics, median LOS was 3 days (IQR: 2–4), with 9 (20.9%) patients having LOS > 4 days, and 30- and 90-day readmission rates of 11.6% and 18.6%, respectively. There were 4 patients (9.3%) with diabetesrelated morbidity and 1 death due to cancer within 90 days.
DISCUSSION
This study reveals several new aspects about type 2 diabetes as a preoperative risk factor in fast-track total THA and TKA. First, although there were about 3% more type 2 diabetics with LOS > 4 days and 90-day readmissions, this was not associated with type 2 diabetes after
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233
Type-2 Diabetics and Fast-Track Hip and Knee Arthroplasty Table 2. Patient Characteristics Variable Age median (IQR) BMI mean (IQR) Female THA Living alone Living in institution Use of walking aid Hypertension Hypercholesterolemia Cardiac disease Antihyperglycemic treatment Insulin Oral only Diet
Type 2 diabetics (n = 890) 69 (64–79) 30.9 (27.7–35.1) 444 (49.9) 372 (41.8) 300 (33.7) 46 (0.6) 287 (32.2) 719 (80.8) 621 (69.8) 185 (20.8) 174 (19.6) 598 (67.2) 118 (13.2)
Nondiabetics (n = 7165) 68 (61–75) 27.5 (24.8–30.9) 4075 (56.9) 3781 (52.8) 2384 (33.3) 11 (1.2) 1741 (24.3) 3616 (50.5) 1804 (25.2) 839 (11.7) N/A
P value
T
he annual number of patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) has been steadily increasing throughout the past decade, with a concomitant increase in number of comorbidities.1 One of the reasons for the increase in comorbidity is the increasing prevalence of diabetes,2 likely due to increased age and prevalence of obesity in the general population and increased lifespan among diabetics in most Western countries.3 Diabetes is a generally acknowledged risk factor for postoperative mortality and morbidity in many types of From the *Section for Surgical Pathophysiology, Rigshospitalet, Copenhagen University, Copenhagen, Denmark; †The Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement, Copenhagen, Denmark; and ‡Department of Endocrinology, Hvidovre University Hospital, Copenhagen University, Copenhagen, Denmark. §The members of the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Collaborative Group are coauthors of this study and are listed in the Appendix. Accepted for publication July 9, 2014. Funding: This work was sponsored by a grant (grant number R25-A2702) from the Lundbeck Foundation, Denmark. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Christoffer C. Jørgensen, MD, Section for Surgical Pathophysiology, Rigshospitalet, Blegdamsvej 9 2100, Copenhagen, Denmark. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/ANE.0000000000000451
230 www.anesthesia-analgesia.org
surgeries.4,5 This also applies to major joint arthroplasty,6–8 although a few recent studies have been unable to demonstrate such association.9,10 Furthermore, pre- and perioperative hyperglycemia are independent predictors of postoperative morbidity after noncardiac surgery5 and specifically after major joint arthroplasty.6,11,12 This finding has led to suggestions of aggressive postoperative glycemic control,13 despite concerns about the increasing risk of hypoglycemia.14 Consequently, specific considerations regarding the perioperative continuum of care in the diabetic patient14,15 and increased focus on perioperative blood glucose management are recommended.16,17 No previous studies of THA and TKA in diabetics have been done in a standardized fast-track setting with optimized perioperative care, including spinal anesthesia, opioid-sparing multimodal analgesia, early mobilization, and discharge to home, which improved outcome after surgery.18 Because the fast-track approach has also been shown to reduce postoperative insulin resistance,19 there is a need to clarify the role of preoperative diabetes in fast-track surgery20 and to elucidate which types of postoperative morbidities occur in these potential high-risk patients.21 Using prospectively collected data, we investigated the association between diabetes and length of hospital stay (LOS) > 4 days, 30- and 90-day readmissions, and mortality in 8055 unselected patients undergoing primary elective unilateral THA and TKA with a standardized fast-track January 2015 • Volume 120 • Number 1
approach. We also studied whether there was an association between the intensity of antihyperglycemic treatment (insulin, oral antihyperglycemics, and diet treatment) and LOS > 4 days and readmissions. Finally, we estimated the number of surgical type 2 diabetics needed for 1 additional case of LOS > 4 days and readmissions (the adjusted number needed to harm [NNH]),22,23 thereby providing a more clinically oriented measure of the specific influence of diabetes on postoperative outcomes after fast-track THA and TKA.
METHODS
All data were collected from 7 departments between February 1, 2010, and November 30, 2012. No approval was needed from the Regional Ethics Committee because this was an analytic observational cohort study using existing prospectively collected data. Permission was acquired from the Danish Data Protection Agency and the Danish National Board of Health to review and store deidentified medical records without informed authorization of release of protected health information.
Preoperative Data
From February 1, 2010, all patients undergoing elective primary THA or TKA at hospitals participating in the Lundbeck Foundation Centre for Hip and Knee Replacement Collaboration have been completing a simple preoperative questionnaire on various patient characteristics. These include body mass index (BMI), living alone/with others, preoperative use of walking aids (yes/no), and known comorbidity such as type 1 and type 2 diabetes, pharmacologically treated cardiac disease, hypercholesterolemia, and hypertension. Staff is available for completing the questionnaire, and completeness of data is >95% of all procedures performed at the participating departments.24 Data are stored in the Lundbeck Foundation Centre database, which is registered as an ongoing study registry on preoperative risk factors on ClinicalTrials.gov (ID: NCT01515670). For this study, further information on specific pharmacologic antihyperglycemic treatment 6 months before surgery was acquired through the Danish National Database of Reimbursed Prescriptions, which registers all prescriptions with reimbursements dispensed at Danish pharmacies.25 In Denmark, all antihyperglycemic medications are reimbursed, and the use of prescription databases has been shown to have a positive predictive value of 98% for type 2 diabetics using oral antihyperglycemics.26 If patients reported type 2 diabetes but had no prescriptions in the Danish National Database of Reimbursed Prescriptions, they were considered as having “diet treatment.” Thirty-six patients didn’t report diabetes but had prescriptions on antihyperglycemic drugs and were thus classified as diabetics.
Perioperative Treatment
The participating departments all used a similar perioperative fast-track approach, including spinal anesthesia, opioid-sparing multimodal analgesia, minimal use of drains and catheters, mobilization on day of surgery, and functional discharge criteria.27 Median LOS of 2 to 3 days until discharge to home has been reported in a smaller cohort included in this study.24
January 2015 • Volume 120 • Number 1
Preoperative evaluation of diabetic status (HbA1C or fasting glucose) was at the discretion of the consulting anesthesiologist. Diabetic patients were typically scheduled for surgery early in the day and intraoperative use of 50 to 100 mL/h of IV glucose (5%)-insulin-potassium or glucose (5%)-insulin was standard in all departments. Intraoperative blood glucose was monitored each hour followed by appropriate adjustments of infusion rate of glucose and insulin. An intraoperative blood glucose >5 and 4 days was chosen as the cutoff for “prolonged” hospitalization because we have previously established that >80% of patients are discharged within 4 days, suggesting that patients with longer LOS have had complications.24 In case of transfer between hospitals/departments, LOS > 4 days, or 90-day readmissions, discharge forms and medical charts were consulted to determine primary reasons for these occurrences. Causes of in-hospital mortality were evaluated using the complete medical charts and autopsy reports if available. Causes of mortality outside hospital were evaluated using death certificates and/or autopsy reports if available. Finally, we constructed a composite outcome of “diabetes-related” morbidity, defined as the occurrence of specific postoperative morbidity more frequently occurring in diabetics than in nondiabetics4,6–8,29 or due to common diabetesinduced organ dysfunctions, and resulting in LOS > 4 days or readmissions. This included any case of cardiac arrhythmia, acute congestive heart failure, myocardial infarction, prosthetic or wound infections, renal insufficiency, cerebral attacks (transient ischemic attacks or cerebral stroke), pneumonia, and urinary tract infection causing LOS > 4 days or readmissions, as well as sepsis and dysregulated blood glucose causing LOS > 4 days and “other infections” causing readmission. All categories of outcome variables were predefined before data analysis (Table 1).
Study Outcomes
Our primary aim was to investigate the association of diabetes and LOS > 4 days, readmissions, and mortality within 90 days postoperatively, both overall and related to antihyperglycemic treatment regimens.
www.anesthesia-analgesia.org
231
Type-2 Diabetics and Fast-Track Hip and Knee Arthroplasty Table 1. Definitions of Complications Causes of LOS > 4 days Category Complications related to general or spinal anesthesia, postanesthetic Anesthetic cramps, difficulties with intubation, etc. complications Wound-related infections Prosthetic infections Hip displacements during admission Hip displacement Symptomatic DVT or PE DVT/PE Low hemoglobin leading to blood transfusion or continued observation Anemia Dizziness during mobilization with normal fluid balance and hemoglobin Dizziness/OI Surgically related pain and pain of other causes Pain (chronic pain patients, back pain, etc.) Falls Falls Side effects of pain treatment or other medication; prolonged Medication/ mobilization without further explanation mobilization Arterial thrombosis, fractures without trauma, intrasurgical Other surgical complications, prosthesis malfunction, bleeding sequelae episodes, swelling, and hematomas Arrhythmias, heart insufficiency, myocardial infarctions, low blood Cardiac pressure related to preoperative severe heart disease Pneumonia, chronic obstructive lung disease, dyspnea, atelectasis Pulmonary Ischemic stroke and other infarctions, transient cerebral ischemia, Cerebral delirium, preoperative neurologic, or psychiatric disease Ileus, dyspepsia, gastritis, gastric ulcers and other gastrointestinal Gastrointestinal bleeds, obstipation Renal insufficiency, dehydration, potassium or sodium Renal outside reference values Urinary retention, problems with urinary catheters, urinary tract Urologic infections Severe infection resulting in multiple organ affection and Sepsis described as a state of sepsis in discharge papers Sleep apnea, dysregulated blood glucoses, symptoms Other medical sequelae of addisonian crisis, dysregulated regular anticoagulant treatment Social reasons for continued admission, other elective Social/unrelated surgery during admission, preoperative hemophilia, causes unspecified symptoms with no diagnoses Standard discharge papers stating successful No morbidity surgery and rehabilitation Causes of 90-day readmissions Prosthetic infection treated with revision, wound incision, or IV antibiotics Hip displacements without falls Surgery due to unsatisfactory mobility of the knee Revision surgery due to prosthesis malfunction or suboptimal placement Description of prosthesis-related fracture without any preceding trauma Wound complications, hematoma, muscle rupture, other reoperations, arterial thrombosis DVT or PE confirmed by US, CT, or lung scintigraphy Symptoms of anemia followed by blood transfusion Pain in relation to recent surgery Falls mentioned as reason for admission regardless of injury Need of further rehabilitation, dizziness, nausea, and obstipation associated with opioid use Arrhythmias, myocardial infarction, heart insufficiency, and unverified acute coronary syndrome with no other apparent diagnosis Pneumonia, worsening of chronic obstructive lung disease,a dyspnea Transient cerebral ischemia, stroke, cerebral bleeds Ileus, gastric ulcers or gastritis, obstipation unrelated to opioid treatment, diarrhea Renal insufficiency Urinary tract infection,a urinary retention, hematuria Other types of infections, syncope,a unspecific indisposition DVT or PE not found and no other treatment prescribed Suspected, but unconfirmed infection and no antibiotic treatment prescribed
Category Prosthetic infections
Included as “diabetes-specific morbidity”
All cases
Only arrhythmias, heart insufficiency, and myocardial infarctions Only pneumonias Only strokes, infarctions, and transient cerebral ischemia
Only renal insufficiency and dehydration Only urinary tract infections All cases Only dysregulated blood glucoses
Included as “diabetes-specific morbidity” All cases
Hip displacement Knee manipulation Revision Fracture without trauma Other surgical sequelae DVT/PE Anemia Pain Falls Medication/mobilization Cardiac Pulmonary Cerebral Gastrointestinal Renal Urologic Other medical sequelae Unverified DVT/PE Unverified wound infection
Only arrhythmias, heart insufficiency, and myocardial infarctions Only pneumonia All cases
All cases Only urinary tract infection Only other types of infections
DVT = Deep venous thrombosis; PE = pulmonary embolism; US = ultrasound; CT = computer tomography; LOS = length of stay; OI = orthostatic intolerance. a Included for the first 30 days only.
232 www.anesthesia-analgesia.org
anesthesia & analgesia
Our second aim was to determine the relationship between preexisting diabetes and its treatment regimen and the occurrence of “diabetes-related morbidity” postoperatively, with an adjusted NNH22,23 for both LOS > 4 days, 30- and 90-day readmissions, and “diabetes-related comorbidity.” The adjusted NNH is the number of surgical type 2 diabetics needed for 1 more case of LOS > 4 days, readmission, or diabetes-related morbidity related specifically to the presence of diabetes while controlling for other confounders.22,23 During data preparation, we found that there were too few patients with type 1 diabetes to include them in the main analyses. Crude results for these few patients are therefore reported separately.
Statistics
Distribution of data was assessed using KolmogorovSmirnov with Lilliefors correction. Nonparametric data are reported as medians with interquartile ranges (IQR). MannWhitney U test was used for unadjusted analysis of nonparametric data, while χ2 test and Fisher exact test were used for categorical data when appropriate. To adjust for baseline differences between type 2 diabetics and nondiabetics, we calculated propensity scores30 using logistic regression with type 2 diabetes as outcome and age, sex, BMI, use of walking aids, operated joint, living alone/in institution/with others, pharmacologically treated cardiac disease, treated hypertension, and treated hypercholesterolemia as covariates. Age and BMI were entered as continuous covariates, while 2 separate variables were created regarding living alone or in institution using living with others as reference. The remaining variables were dichotomized (present/not present) with type 2 diabetes treatment categorized as insulin (with/without oral treatment), oral antihyperglycemic drugs only, and diet only (no pharmacologic treatment) versus nondiabetics for subanalyses. Of 8804 consecutive surgical patients, we initially excluded 36 (0.4%) due to missing information on diabetic status. Of the remaining 8768 procedures with completed preoperative questionnaires and information on diabetes, 43 (0.5%) procedures were in type 1 diabetics and 957 were in type 2 diabetics (10.9%). The percentage of type 2 diabetics was 9.3%–12.7% of all procedures in the different departments. It was possible to calculate propensity scores for 890 (93.0%) procedures in type 2 diabetics and for 7414 (95.4%) in nondiabetics. The C-statistic for the propensity model was 0.82, indicating a satisfactory predictive power. Trimming of the data set was performed to further improve accuracy of the model by excluding 249 procedures (3.0%) for which there was no propensity score overlap between groups.31 Thus, the final study population consisted of 890 (11.0%) procedures in type 2 diabetics and 7165 (89.0%) in nondiabetics. Analysis on outcomes was done using multiple logistic regressions, adjusting for patient characteristics and for propensity score as a continuous variable in a “doubly robust” model.30 Department of surgery (dichotomized into those with significantly more readmissions than the department with the fewest versus others) was also included in the multiple regression analysis to adjust for potential logistical and
January 2015 • Volume 120 • Number 1
population differences not otherwise accounted for in the standardized perioperative setup. Only the first readmission was included for regression analysis. We also tested for relevant interactions using pairwise separate models and applying the Wald test statistics. Results are reported as adjusted odds ratios (OR) with 95% confidence intervals (95% CI) and a 2-tailed P-value of 4 days (unadjusted P = 0.001; Fig. 1, A), there was no association between LOS > 4 days and type 2 diabetes when adjusting for covariates. This was regardless of antihyperglycemic treatment (Table 3). When comparing the causes of LOS > 4 days, renal, urologic, and cerebral complications were significantly more frequent in type 2 diabetics (Table 4). Readmissions within 30 and 90 days were both more frequent in type 2 diabetics (6.5% and 10.2%) than in nondiabetics (5.5% and 7.8%) (Fig. 1, B and C). However, after adjusting for covariates, no association between type 2 diabetes and 30- or 90-day readmissions was found (Table 3). Renal and urologic complications reoccurred more frequently in type 2 diabetics (Table 4). Finally, 90-day all-cause mortality was 0.3% in both type 2 diabetics (n = 3) and in nondiabetics (n = 23).
Secondary Outcomes, Diabetes-Related Morbidity, and Adjusted Number Needed to Harm
The composite outcome of diabetes-related morbidity occurred in 6.0% of type 2 diabetics and in 3.6% of nondiabetics. (Fig. 1, D). After covariate adjustment, only insulintreated type 2 diabetes was found to be associated with diabetes-related morbidity (Table 3). Because there was no significant association between type 2 diabetes and study outcomes, infinity was included in all estimates of the adjusted NNH (Table 3).
Type 1 Diabetics
In the 43 excluded type 1 diabetics, median LOS was 3 days (IQR: 2–4), with 9 (20.9%) patients having LOS > 4 days, and 30- and 90-day readmission rates of 11.6% and 18.6%, respectively. There were 4 patients (9.3%) with diabetesrelated morbidity and 1 death due to cancer within 90 days.
DISCUSSION
This study reveals several new aspects about type 2 diabetes as a preoperative risk factor in fast-track total THA and TKA. First, although there were about 3% more type 2 diabetics with LOS > 4 days and 90-day readmissions, this was not associated with type 2 diabetes after
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Type-2 Diabetics and Fast-Track Hip and Knee Arthroplasty Table 2. Patient Characteristics Variable Age median (IQR) BMI mean (IQR) Female THA Living alone Living in institution Use of walking aid Hypertension Hypercholesterolemia Cardiac disease Antihyperglycemic treatment Insulin Oral only Diet
Type 2 diabetics (n = 890) 69 (64–79) 30.9 (27.7–35.1) 444 (49.9) 372 (41.8) 300 (33.7) 46 (0.6) 287 (32.2) 719 (80.8) 621 (69.8) 185 (20.8) 174 (19.6) 598 (67.2) 118 (13.2)
Nondiabetics (n = 7165) 68 (61–75) 27.5 (24.8–30.9) 4075 (56.9) 3781 (52.8) 2384 (33.3) 11 (1.2) 1741 (24.3) 3616 (50.5) 1804 (25.2) 839 (11.7) N/A
P value
