Update in Perioperative Medicine Electronic Handout - SGIMimpak.sgim.org/userfiles/file/AMHandouts/AM05/handouts/CU06.pdf · – Preop; postop days 1,3,7,d/c • CPK, ... • 35 periop

UPDATE IN PERIOPERATIVE MEDICINE

2005

Steven L. Cohn, MD, FACPGerald W. Smetana, MD, FACP

Amir Jaffer, MDHarrison G. Weed, MD, MS, FACP

Perioperative Cardiac Medicine

Steven L. Cohn, MD, FACPChief – Division of General Internal Medicine

Director – Medical Consultation ServiceClinical Professor of Medicine

SUNY Downstate

Perioperative Cardiac Medicine

• Preoperative Cardiac Risk Evaluation– Nothing new

• Perioperative Risk Reduction Strategies– PCI/CABG– Medical Therapy

• Statins, beta-blockers, clonidine

• Future Studies– POISE, DECREASE IV

PCI/CABG Coronary Artery Revascularization before Elective

Major Vascular Surgery (CARP Trial)McFalls et al. N Engl J Med 2004;351:2795-2804

• Goal: Benefit of prophylactic revascularization• Primary endpoint: long-term mortality • 5859 pts – elective AAA or severe arterial occlusive

disease• Excluded initially – 4669 pts (80%)

– Insufficient cardiac risk: 1654– Urgent/emergent surgery: 1025– Severe co-existing illness: 731– Prior revascularization w/o recurrent ischemia:626– Decision not to participate/ineligible: 633

CARP Study Design5859 pts screened

1190 angiography

510 study pts

252 No Revasc258 Revasc

18 didn’t go 9 req revasc99 CABG141 PCI

9 refused8 urgent surg1 CVA waiting

10 died

4669 excluded

680 excluded

CARP Angio Results(n=1119)

• Angio findings of 680 excluded pts (57%)– Non-obstructing lesions – 363 (53%)– Not amenable to revasc – 215 (32%)– Left main – 54 (8%)– LVEF <20% - 11 (2%)– Severe AS – 8 (1%)– Refused cath – 29 (4%)

• Angio findings in study pts (n=510)– 33% each for 1, 2 or 3 vessel disease– 15% had prior CABG

CARP: Vascular Surgery

18 days54 days48 days post-CABG

41 days post-PCI

Timing of surgpost-random(median)

237 (94%)1 died (CABG), 9

refused, 5 med cond

225 (87%)10 died, 8 refused, 5

med condition

Had vascular surgery

No revasc(n=252)

Revasc(n=258)

CARP Patient Characteristics• Eagle criteria (comparable in both groups)

– Prior MI – 41-43%– Angina – 38-39%– DM – 38-40%– CHF – 8-12%– Age >70 – 60%– >3 risk factors – 28%; 1 or 2 plus isch NIT – 65%

• Revised Cardiac Risk Index– >2: 49%; >3: 13%

• NIT (nuclear) perfusion defect– Mod-large: 226/316 - 72%

CARP Post-Procedural Complications(post-CABG or PCI w/i 30 days)

%(n=240)

Complication

0%CVA/loss of limb/dialysis

2.5%(6)

Reoperation

5.8%(14)

MI

1.7%(4)

Mortality

CARP Outcomes

21 (8%)Required later revasc

67 (23%)70 (22%)Long-term death*(2.7 yrs after random)

34 (14%)20 (8%)

26 (12%)19 (8%)

Postop MI: enzymesenzymes and ECG

8 (3%)7 (3%)Death w/i 30 d of surg

110Death before surgery

No revasc(n=237)

Revasc(n=225)

* No difference when comparing assigned vs received treatment.

CARP Conclusion• Coronary artery revascularization before

elective vascular surgery among patients with stable cardiac symptoms does not significantly alter outcome, and on the basis of these data, cannot be recommended (ie, the ACC was right!).

• Caveats: – Both groups received intensive medical therapy

(84% beta-blockers, 54% statins, 51% ACE-I, 73% ASA, 93% heparin).

– Limitations: men, VA Hosp, not powered to detect beneficial short-term effect

PCIDoes Preoperative Coronary Angioplasty Improve Perioperative Cardiac Outcome?

Godot et al. Anesthesiology 2005;102:739-746

• 1152 pts (78 pts had PCI) – AAA repair• Propensity score analysis, logistic regression model• Outcome: severe coronary event or postop death• 5 independent predictors for each outcome• No difference between PCI pts and expected

outcome for overall group• Conclusion: PCI did not seem to significantly limit

cardiac risk or death after aortic surgery.

Does Preoperative Coronary Angioplasty Improve Perioperative Cardiac Outcome?

Godot et al. Anesthesiology 2005;102:739-746

Previous CHFPrevious CHFRepeated surgeryRepeated surgery

ExpectedPCI 5.1% (CI 2.0-12.5)9% (CI 4.4-17.4)

6.9%8.2%

Previous HTNPreop hemodialysis

Previous abnormal ST-T changes

Blood transfusion >3 units

Age >75Age >75

Postop deathSevere coronary event

Summary: Coronary Stents and Noncardiac Surgery

6 wks35456Reddy(2005)

6 wks236207Wilson(2003)

24(6.9%)

8

11

Bleeding

4 wks

2 wks

Recom

4647Sharma(2004)

19(5.4%)

24(6.9%)

350TOTALS

7840Kaluza(2000)

MIDeath# ptsStudy

Medical Therapy: StatinsStatins Decrease Perioperative Cardiac Complications in Patients Undergoing Noncardiac Vascular Surgery: Statins for Risk Reduction in Surgery (StaRRS) Study

O’Neill-Callahan et al. J Am Coll Cardiol 2005;45:336-342

• Retrospective, 1163 hospitalizations, 997 pts• CEA, aortic surgery, low extrem revascularization• Outcomes: death, MI, ischemia, CHF, VT• Univariate and multivariate analyses• Statin use reduced complication rates including in

the multivariate model accounting for:– age, gender, BMI, type of surgery, urgency, LV

dysfunction, DM

Medical Therapy: StatinsStaRRS Study

• OR 0.56 for all complications (CI .39-.79) as well as for combined death, MI, and ischemia (CI .31-.99; p=0.046).

• Beta-blocker OR 0.96• CONCLUSION: Preoperative statin use significantly

decreased cardiovascular complications.

VTCHFOther ischemiaMIDeath

Complication Outcomes (n=157)

13 (2.5%)21 (3.9%)5 (1.0%)7 (1.3%)6 (1.1%)

Statins (526)(n=52; 9.9%)

17 (4.6%)50 (7.8%)26 (4.1%)7 (1.1%)5 (1.4%)

No Statins (637)(n=105; 16.5%)

Medical Therapy: StatinsSafety of Perioperative Statin Use in High-risk Patients

Undergoing Major Vascular SurgerySchouten et al. Am J Cardiol 2005;95:658-660

• Retrospective, 981 vasc surgery pts screened• Acute vs long-term vs no statin use• Confounders for myopathy evaluated

– Length of surgery, other meds, liver dysfunction, statin dose, hypothyroidism

• Assessed muscle complaints (weak/pain)– Preop; postop days 1,3,7,d/c

• CPK, CPK-MB, AST, ALT, troponin T, ECG


Undergoing Major Vascular Surgery

• 981 pts – excluded 98 (9.8%) with periop MI• 81 non-user (10.8%) and 15 statin users (6.7%)

• 35 periop deaths (none from rhabdo)• 30 non-users (3.9%) and 5 statin users (2.1%)

• Endpoint of periop death or MI:– 111 non-statin users (14.7%)– 22 statin users (8.8%)*

* p<0.01


Undergoing Major Vascular Surgery

10%8%>10 x ULN192301Median max CPK*

6%9%>5 x, <10 x ULN33%43%>1 x, <5 x ULN51%40%<1 x ULN

Non-user(n=674)

Statin user (n=211)

Postop CPK

* p=0.003 but difference bet users/non-users not significant (p=0.142)

Only risk factor was length of surgery

CONCLUSION: No association between long-term, acute use, or dose and CPK–no rhabdo.

Medical Therapy: Beta-blockers Diabetic Postoperative Mortality and Morbidity (DIPOM) Trial

Juul et al. 2004 Late-breaking Trial (ACC)

• Randomized, placebo-controlled blinded multicenter trial

• 921 beta-blocker naïve diabetic ptsundergoing noncardiac surgery

• Metoprolol vs placebo (max 8 days)• Primary outcome: composite all-cause

mortality, MI, UA, CHF

Medical Therapy: Beta-blockers Diabetic Postoperative Mortality and Morbidity

(DIPOM) Trial

• Heart rate lower with metoprolol (72 vs 78 bpm)• Primary outcome:

– 21% metoprolol group vs 20% placebo group• Intent to treat multivariate analysis

– Hazard ratio 1.10 (p=0.53)• Conclusion: Short-term metoprolol did not

significantly alter mortality or cardiac morbidity in diabetic patients undergoing noncardiac surgery (but wide CI).

Medical Therapy: Clonidine Effect of Clonidine on Cardiovascular Morbidity and

Mortality after Noncardiac SurgeryWallace et al. Anesthesiology 2004;101:284-293

• Prospective double-blind trial• 190 pts with CAD or risk factors undergoing

elective noncardiac surgery• Clonidine (0.2 mg PO + patch) vs placebo• Duration: night before for 4 days• Outcome: perioperative ischemia and long

term mortality

Medical Therapy: Clonidine Effect of Clonidine on Cardiovascular Morbidity

and Mortality after Noncardiac Surgery

NS9.2-10.7%4.0-6.4%In-hosp hard events(MI,CHF,UA,VT,CVA)

0.035**29.2%15.2%2 year mortality

0.048**6.2%0.8%30 day mortality

0.01*31%14%Ischemia(intraop to POD #3)

P valuePlacebo(n=65)

Clonidine(n=125)

Outcomes

(After removing beta-blocker use: * Unchanged; ** NS )

Future Studies

• POISE (Devereaux) – prophylactic beta-blockers vs placebo in >8000 ptsundergoing various types of noncardiac surgery

• DECREASE IV (Poldermans) – fluvastatin and bisoprolol to reduce cardiac morbidity and mortality in high-risk patients undergoing noncardiac surgery

SUMMARY• Nothing new for preop risk evaluation.• Prophylactic PCI/CABG did not improve outcome.• Complication rate of noncardiac surgery within 2-

6 weeks of PCI is significant.• Statins appear to lower perioperative morbidity

and mortality as well as being safe.• Beta-blockers may not be as effective as initially

reported in reducing perioperative risk.• Clonidine may reduce ischemia and death, and

may be an alternative to beta-blockers.

Update in Perioperative Medicine Update in Perioperative Medicine Pulmonary EvaluationPulmonary EvaluationSGIM Annual Session: May 2005SGIM Annual Session: May 2005

Gerald W. Smetana, M.D.Gerald W. Smetana, M.D.Division of General Medicine Division of General Medicine Beth Israel Deaconess Medical Center, BostonBeth Israel Deaconess Medical Center, Boston

American College of PhysiciansAmerican College of PhysiciansPreoperative Pulmonary Evaluation Preoperative Pulmonary Evaluation Position Statement (Draft)Position Statement (Draft)

Smetana GW, Lawrence VA, Cornell JESmetana GW, Lawrence VA, Cornell JESystematic review of literature dating to Systematic review of literature dating to 1980 as background paper for ACP 1980 as background paper for ACP position statementposition statementObjective: Systematic review of the Objective: Systematic review of the evidence regarding risk factors, laboratory evidence regarding risk factors, laboratory testing, and preventive strategies for testing, and preventive strategies for postoperative pulmonary complicationspostoperative pulmonary complications

Study SelectionStudy Selection

Inclusion criteriaInclusion criteria19801980--20032003English languageEnglish languageEvaluated clinical PPCs Evaluated clinical PPCs rather than physiologic rather than physiologic outcomesoutcomesExplicit definition of Explicit definition of PPCsPPCsSystematic reviewsSystematic reviewsOriginal dataOriginal data

Exclusion criteriaExclusion criteriaEditorials, lettersEditorials, lettersAdministrative data onlyAdministrative data only< 25 patients < 25 patients Developing countriesDeveloping countriesCardiopulmonary Cardiopulmonary surgerysurgeryPediatric surgeryPediatric surgeryOrgan transplantationOrgan transplantation

Methods: Methods: Clinically Clinically Important Important PPCsPPCs

• PneumoniaPneumonia

•• Respiratory Respiratory failurefailure

•• AtelectasisAtelectasis

•• COPD COPD exacerbationexacerbation

Statistical MethodsStatistical Methods

Retrieved primarily observational studiesRetrieved primarily observational studiesPooled metaPooled meta--analyses of relative risks from analyses of relative risks from univariate studies using random effects univariate studies using random effects modelsmodelsBias adjusted univariate dataBias adjusted univariate dataEstimates of publication biasEstimates of publication biasMultivariable analyses were too Multivariable analyses were too heterogeneous to perform metaheterogeneous to perform meta--analysisanalysisTabulated frequency of significant factors Tabulated frequency of significant factors among eligible MV analysesamong eligible MV analyses

Total Citations 15,499

Duplicate 1,165

Eligible Studies325

Citations Screened by Title and Abstract

14,334Not Relevant or

Met Exclusion Criteria13,461

Full Article Reviewed873

Not Relevant or Met Exclusion Criteria 54813 – Cardiac or pulmonary surgery13 Physiologic outcomes only14 – Non-RCT intervention study47 – Ineligible publication type 52 – N < 25 per arm70 – Miscellaneous339 -Inadequate PPC definition or data

Univariate Analyses88

Multivariable Analyses

32

Randomized Trialsand Systematic Reviews

30 / 11

Background164

Results Vary By Study SizeResults Vary By Study Size

PPC rates varied with study sizePPC rates varied with study sizeStudies with < 500 patientsStudies with < 500 patients–– Median PPC rate 14% (CI 8.7Median PPC rate 14% (CI 8.7--25)25)

Studies with > 500 patientsStudies with > 500 patients–– Median PPC rate 4% (CI 2.6Median PPC rate 4% (CI 2.6--6.3)6.3)

Lower PPC Rates in Larger Lower PPC Rates in Larger StudiesStudies

0.2

.4.6

.8

2 3 4 5 2 3 4 5

Univariate Multivariable

Study Specific PPC rate Median Spline

PP

C R

ate

Study Size (log N)

Graphs by Univariate and Multivariable Studies

PatientPatient--Related Risk FactorsRelated Risk Factors

227.457.45ASA class >2ASA class >2

22Abnormal CXRAbnormal CXR

33Functional dependenceFunctional dependence

33Poor exercise capacityPoor exercise capacity

661.891.89CigarettesCigarettes

2.772.77Age > 70Age > 70

1.991.99Age > 65Age > 65

10101.871.87Age > 60Age > 60

13131.36 1.36 COPDCOPD

# Significant MV # Significant MV StudiesStudies

Univariate Bias Univariate Bias Adjusted OR Adjusted OR

FactorFactor

ProcedureProcedure--Related Risk FactorsRelated Risk Factors

331.291.29VascularVascular442.302.30--3.103.100.990.99Head and neckHead and neck442.502.50--3.633.630.870.87Any abdominalAny abdominal553.923.92--8.148.14ThoracicThoracic554.294.29--14.314.31.671.67AorticAortic771.331.33--3.603.600.690.69Emergency surgeryEmergency surgery881.561.56--5.705.701.361.36General anesthesiaGeneral anesthesia882.682.68--8.148.141.631.63Upper abdominalUpper abdominal12121.061.06--3.223.222.782.78Prolonged surgeryProlonged surgery

# MV # MV Significant Significant StudiesStudies

MV ORMV ORUnivariate Univariate Bias Bias Adjusted ORAdjusted OR

Most Frequently Cited Risk Factors in Most Frequently Cited Risk Factors in Multivariable AnalysesMultivariable Analyses

NANA9933Abnormal spirometryAbnormal spirometry

1.561.56--5.75.78833General anesthesiaGeneral anesthesia

3.923.92--8.148.145533Thoracic surgeryThoracic surgery

4.294.29--14.314.35533AAA repairAAA repair

1.831.83--2.832.834433Functionally dependentFunctionally dependent

1.391.39--2.292.293333Elevated BUN or creatElevated BUN or creat

1.331.33--3.63.67744Emergency surgeryEmergency surgery

2.532.535544Albumin < 3 Albumin < 3 gmsgms/dl/dl

2.52.5--3.633.634444AbdominalAbdominal

1.281.28--10.310.3171766Cigarette useCigarette use

2.682.68--8.148.148866Upper abdominalUpper abdominal

1.061.06--3.223.227766Surgery >3Surgery >3--4 hours4 hours

1.511.51--7.247.2421211010Advanced ageAdvanced age

1.721.72--13313315151313COPDCOPD

RR RangeRR Range# Eligible # Eligible StudiesStudies

# Studies Reporting # Studies Reporting SignificanceSignificance

FactorFactor

Summary Grades: DefinitionsSummary Grades: Definitions

Good evidence to support excluding the risk factor. Good evidence to support excluding the risk factor. Harm outweighs benefitHarm outweighs benefit

EE

Fair evidence to support excluding the risk factor. Fair evidence to support excluding the risk factor. Harm outweighs the benefit.Harm outweighs the benefit.

DD

Insufficient evidence. Balance of benefit and harm is Insufficient evidence. Balance of benefit and harm is too close to justify a recommendationtoo close to justify a recommendation

CC

Fair evidence to support the risk factor or intervention. Fair evidence to support the risk factor or intervention. The benefit outweighs the harmThe benefit outweighs the harm

BB

Good evidence to support the risk factor or Good evidence to support the risk factor or intervention. For interventions, benefit outweighs intervention. For interventions, benefit outweighs harmharm

AA

DefinitionDefinitionGradeGrade

Grade A Risk FactorsGrade A Risk Factors

Thoracic surgeryThoracic surgeryAlbumin < 3 gm/dlAlbumin < 3 gm/dl

AAA repairAAA repairLaboratory testingLaboratory testing

Emergency surgeryEmergency surgeryASA class > 2ASA class > 2

Any abdominalAny abdominalFunctionally dependentFunctionally dependent

Upper abdominalUpper abdominalAdvanced ageAdvanced age

Prolonged surgeryProlonged surgeryCOPDCOPD

ProcedureProcedure--RelatedRelatedPatientPatient--RelatedRelated

Grade BGrade B--E Risk FactorsE Risk Factors

BBElevated BUN or creatElevated BUN or creatCCDiabetesDiabetes

CCSpirometrySpirometryBBCXRCXREEObesityObesity

Laboratory testingLaboratory testingCCWeight lossWeight lossCCTransverse Transverse abdabd incisionincisionCCArrhythmiaArrhythmiaCCLaparoscopic surgeryLaparoscopic surgeryCCAlcohol useAlcohol useCCVascular surgeryVascular surgeryCCCorticosteroid useCorticosteroid useCCTransfusionTransfusionBBCigarette useCigarette useBBPancuronium usePancuronium useBBPoor exercise capacityPoor exercise capacityBBEsophageal surgeryEsophageal surgeryBBAbnormal chest examAbnormal chest examBBNeurosurgeryNeurosurgeryBBCHFCHFBBNeck surgeryNeck surgeryBBImpaired sensoriumImpaired sensoriumBBGeneral anesthesiaGeneral anesthesiaBBObstructive sleep apneaObstructive sleep apneaGradeGradeProcedureProcedure--RelatedRelatedGradeGradePatientPatient--RelatedRelated

SpirometrySpirometry

13 eligible studies of spirometry13 eligible studies of spirometry3 of 4 multivariable studies found FEV1 to 3 of 4 multivariable studies found FEV1 to predict PPC ratespredict PPC ratesFew studies compared FEV1 to history and Few studies compared FEV1 to history and physical examination or adjusted for this in physical examination or adjusted for this in MV analysisMV analysisStrength of recommendation: CStrength of recommendation: C

Potential Risk Reduction StrategiesPotential Risk Reduction Strategies

Lung specificLung specific–– Cigarette cessationCigarette cessation–– Lung expansion Lung expansion

modalitiesmodalities

Anesthesia techniqueAnesthesia technique–– Neuromuscular blockadeNeuromuscular blockade–– Neuraxial anesthesiaNeuraxial anesthesia–– Postop analgesiaPostop analgesia

Surgical techniqueSurgical technique–– Midline vs. transverse Midline vs. transverse

abdominal incisionabdominal incision–– Laparoscopic vs. open Laparoscopic vs. open

abdominal surgeryabdominal surgery

Perioperative carePerioperative care–– TransfusionTransfusion–– Pharmacologic Pharmacologic

interventionsinterventions–– Nutritional supportNutritional support–– PA cathetersPA catheters–– NG decompressionNG decompression

Risk Reduction StrategiesRisk Reduction Strategies

EERight heart catheterizationRight heart catheterization

DDTotal enteral nutritionTotal enteral nutrition

DDTotal parenteral nutritionTotal parenteral nutrition

CCLaparoscopic surgeryLaparoscopic surgery

BBEpidural analgesiaEpidural analgesia

BBShort acting neuromuscular blockerShort acting neuromuscular blocker

BBSmoking cessationSmoking cessation

AASelective postop nasogastric tubeSelective postop nasogastric tube

AALung expansion maneuversLung expansion maneuvers

Strength of Strength of RecommendationRecommendation

StrategyStrategy

LimitationsLimitations

Many studies too small to capture important Many studies too small to capture important PPCsPPCsUnivariate studies dominate literature and Univariate studies dominate literature and subject to biasessubject to biasesMV studies variably report factors included in MV studies variably report factors included in modelsmodelsThree large VA studies drive the summary Three large VA studies drive the summary estimatesestimates

ConclusionsConclusions

Reaffirm value of traditional PPC risk factorsReaffirm value of traditional PPC risk factorsConfirm importance of surgical siteConfirm importance of surgical siteNovel risks include albumin < 3, routine NG Novel risks include albumin < 3, routine NG decompressiondecompressionLimited role for preoperative spirometryLimited role for preoperative spirometryIdentify specific risk reduction strategiesIdentify specific risk reduction strategiesAreas for future researchAreas for future research–– Large studies for stable PPC estimatesLarge studies for stable PPC estimates–– MV analyses for risk factor assessmentsMV analyses for risk factor assessments–– RCTsRCTs for risk reduction strategiesfor risk reduction strategies

Update in Perioperative MedicineVenous Thromboembolism Prophylaxis/Anticoagulation

Society of General Internal Medicine MeetingNew Orleans, LAMay 12 , 2005

Amir Jaffer, MDCleveland Clinic Foundation

Medical Director, The IMPACT (Internal Medicine Preoperative Assessment Consultation and Treatment ) Center &

The Anticoagulation ClinicDept. of General Internal Medicine

Section of Hospital & Preoperative Medicine

Disclosures

• Grant & Research Support from Astra Zeneca

• Consultant for Sanofi-Aventis and Astra Zeneca

• Speaker’s Bureau for Sanofi-Aventis

Outline

• What is “sort of new” in the ACCP guidelines with respect to post-operative venous thromboembolism

• VTE after Major Joint Replacement– Warfarin Vs. Enoxaparin for VTE prevention– Association between HRT and post-operative VTE

• Perioperative Anticoagulation Management– Assessment of a standardized LMWH regimen

What is “Sort of New” in the 7th ACCP Conference Guidelines as it relates to

Prevention of Venous Thromboembolism

General Recommendations• Mechanical methods

– High risk of bleeding 1C+– Adjunct to anticoagulant 2A– Proper use and compliance

with mechanical device 1C+• Consider Renal Clearance when deciding on

pharmacologic prophylaxis 1C+• Caution with anticoagulants and Neuroaxial

anesthesia 1C+

What is “Sort of New” in the 7th ACCP Conference Guidelines as it relates to

Prevention of Venous Thromboembolism

• Hip Fracture: Fondaparinux 1A• TKA: LMWH/Warfarin/Fonda 1A• THA: LMWH/Warfarin/Fonda 1A• Extended Prophylaxis for THA/Hip

Fracture for 28-35 days 1A

Enoxaparin Vs. Warfarin for VTE prophylaxis after Major Joint Replacement

• Approx. half a million Major Joint Replacements a year

• Warfarin is still the most common form of prophylaxis in the US

• Recent meta-analyses and RCT’sprovide conflicting information

• Case-control study at a tertiary care center in Cleveland, OH

Mismetti et al. J Thromb Haemos 2004;2:1058Freedman et al. J Bone Joint Surg Am 2000;82-A:929Brotman et al. Thromb Haemost 2004;92;1012-7


Methods• Cases were women >50 yrs who underwent

hip or knee arthroplasty between 1997-2002 and objectively diagnosed with VTE

• Cases (n=84) and Controls (n=206) matched 1:2 according to age, year of surgery, surgeon and type of joint

• Data obtained by chart review• Univariate and Multivariate regression

analysis to determine Odds RatioBrotman et al. Thrombosis and Haemostasis 2004;92:1012-7


Results

P<0.0001

p<0.0001

Brotman et al. Thrombosis and Haemostasis 2004;92:1012-7

Conclusions, Implications and Limitations

• Striking association between warfarin monotherapy and early post-operative VTE

• This association appears plausible• Use alternative parenteral anticoagulant or

consider overlap with warfarin until the INR is therapeutic

• Retrospective, case-control design• Bleeding and wound complications were not

evaluated in this study

Postmenopausal HRT and VTE after Major Joint Replacement

• 57 million users of HRT in the US in 2003• All HRT is associated with VTE• Controversy regarding appropriate

perioperative management of HRT• Case-control study at a tertiary care

center in Cleveland, OH

Hurbanek et al. Thrombosis and Haemostasis 2004;92;337


Methods– 108 female patients > 50 yrs who underwent TKA or THA

and developed post-operative VTE matched by age, date & type of surgery and surgeon with 210 controls without VTE

– Preoperative recommendations and orders were studied to see if HRT use was discontinued

– HRT use was defined as those who continued the drug within 2 weeks of surgery

– Multivariate regression analysis to determine Odds Ratio

Hurbanek et al. Thrombosis and Haemostasis 2004;92;337


Results

• 16.7% of cases had taken HRT

• 23.3% of controls had taken HRT

• Predictors of VTE:prior VTE, rheum disease and absence of pharmacologic prophylaxis

Hurbanek el al. Thrombosis and Haemostasis 2004;92;337


• No association between perioperative HRT and post-operative VTE after major Joint replacement if patients recd. pharmacologic prophylaxis

• The additional risk (pro-thrombotic effect) conferred by HRT in the setting of major joint replacement is extremely small compared to the VTE risk from major joint replacement

• Reasonable to leave women on HRT and SERM’sbefore surgery as long as they receive pharmacologic prophylaxis

• Retrospective case-control design

Hurbanek el al. Thrombosis and Haemostasis 2004;92;337

Assessment of a Standardized Periprocedural Anticoagulation Regimen

• Over 2 million users of warfarin in North America• Certain procedures require interruption of warfarin• Patients with mechanical heart valves or chronic

atrial fibrillation are at high risk for a thromboembolic event

• 7th ACCP guidelines make 2C recommendations using full-dose/prophylactic dose of UFH/LMWH based on thromboembolic risk

• Prospective registry was set up at a tertiary care teaching hospital in Hamilton, ON

Douketis et al. Arch Intern med 2004;164:1319-1326

Assessment of a Standardized Periprocedural Anticoagulation Regimen

Methods– 650 adults requiring interruption of warfarin

therapy for elective surgery or procedure– 215 MHV, 306 Afib, 89 embolic stroke or TIA– Excluded: Cr>2, HIT, pregnancy, minor dental

procedures– Procedures classified according to:

• High bleeding–risk• Non-high bleeding risk

Douketis et al. Arch Intern med 2004;164:1319-1326

Adverse Outcomes Rates

Non-High BleedingRisk Procedure

(n=542)

High-Bleeding Risk Procedure(n=108)

TE (including possible events) 0.74 1.85

Major Bleeding 0.74 1.85

Incr. Wound-related blood loss 5.90 NA

Overall TE = 0.62 (0.17-1.57)Major Bleeding=0.92 (0.34-2.00)

Douketis et al. Arch Intern Med 2004;164:1319-1326


• Low overall incidence of complications• Periprocedural regimen with LMWH is feasible• Study did not have control group• Follow-up limited to 1-week post-op• Subjective classification of procedure into high

bleeding-risk vs. non-high bleeding risk procedure

• RCT is needed

Douketis et al. Arch Intern Med 2004;164:1319-1326

References

1. Geerts, W.H., et al., Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 2004. 126(3 Suppl): p. 338S-400S.

2. Brotman, D.J., et al., Warfarin prophylaxis and venous thromboembolism in the first 5 days following hip and knee arthroplasty. Thromb Haemost, 2004. 92(5): p. 1012-7.

3. Hurbanek, J.G., et al., Postmenopausal hormone replacement and venous thromboembolism following hip and knee arthroplasty.Thromb Haemost, 2004. 92(2): p. 337-43.

4. Douketis, J.D., J.A. Johnson, and A.G. Turpie, Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen.Arch Intern Med, 2004. 164(12): p. 1319-26.

Questions ?

Update in Perioperative Update in Perioperative MedicineMedicine

SGIM, May 2005, New Orleans, LouisianaSGIM, May 2005, New Orleans, Louisiana

Harrison G. Weed, MD, MS, FACPHarrison G. Weed, MD, MS, FACP

Professor of Internal MedicineProfessor of Internal Medicine

The Ohio State University College of MedicineThe Ohio State University College of Medicine

OverviewOverview

•• Future directions in perioperative Future directions in perioperative

medicine research.medicine research.

•• Tight control of hyperglycemia.Tight control of hyperglycemia.

•• Warfarin management for ECT.Warfarin management for ECT.

•• Bleeding with Bleeding with SSRIsSSRIs..

•• Perioperative antimicrobial prophylaxis.Perioperative antimicrobial prophylaxis.

Development of a perioperative Development of a perioperative medicine research agendamedicine research agenda

•• Khan NA, Khan NA, TaherTaher T, McAlister FA, T, McAlister FA, FerlandFerland A, A,

Campbell NR, Campbell NR, GhaliGhali WA.WA.

•• BMC SurgeryBMC Surgery 2004, 2004, 4:4:11 doi:10.1186/147111 doi:10.1186/1471--

24822482--44--1111

•• http://www.biomedcentral.com/1471http://www.biomedcentral.com/1471--2482/4/112482/4/11

Development of a perioperative Development of a perioperative medicine research agenda, Khan, et al.medicine research agenda, Khan, et al.

•• Surveyed general internists:Surveyed general internists:

•• Canadian Society of Internal Medicine (n = 312)Canadian Society of Internal Medicine (n = 312)

•• SGIM perioperative medicine interest group (n = 130)SGIM perioperative medicine interest group (n = 130)

•• 152/442 (34%) responded152/442 (34%) responded

•• 33 subspecialists excluded33 subspecialists excluded

•• Therefore: the opinions of Therefore: the opinions of 119119 general internistsgeneral internists

Development of a perioperative Development of a perioperative medicine research agenda, Khan, et al.medicine research agenda, Khan, et al.

•• 30 research questions30 research questions

•• Presented in random orderPresented in random order

•• Rated each on a 10Rated each on a 10--point scalepoint scale

•• Three research areas:Three research areas:

•• TreatmentTreatment

•• Risk StratificationRisk Stratification

•• Diagnostic TestingDiagnostic Testing

A perioperative research agenda, Khan, et al.A perioperative research agenda, Khan, et al.

•• 8 Highest Rated:8 Highest Rated:•• Tight control of diabetes mellitus.Tight control of diabetes mellitus.

•• Starting aspirin postop. in highStarting aspirin postop. in high--risk patients.risk patients.

•• Continuing aspirin though surgery.Continuing aspirin though surgery.

•• AnticoagAnticoag. management for prosthetic valves.. management for prosthetic valves.

•• ACE inhibitors for highACE inhibitors for high--risk patients.risk patients.

•• Yield of postoperative cardiac surveillance.Yield of postoperative cardiac surveillance.

•• Interventions to minimize postop. delirium.Interventions to minimize postop. delirium.

•• Value of betaValue of beta--blockers.blockers.

ConclusionConclusion

•• Doctors are more interested in Doctors are more interested in

information on treatments to information on treatments to

reduce perioperative risk, than reduce perioperative risk, than

in additional risk stratification.in additional risk stratification.

Insulin therapy for critically ill hospitalized patients: a Insulin therapy for critically ill hospitalized patients: a metameta--analysis of randomized controlled trialsanalysis of randomized controlled trials

Pittas AG, Siegel RD, Lau J.Pittas AG, Siegel RD, Lau J.

Arch Intern Med. 2004 Oct Arch Intern Med. 2004 Oct

11;164(18):200511;164(18):2005--1111

35 randomized, controlled trials35 randomized, controlled trials

published from 1962 to 2002published from 1962 to 2002

Insulin therapy for critically ill hospitalized Insulin therapy for critically ill hospitalized patients: a metapatients: a meta--analysisanalysis

Mortality RR 0.85 (0.75 Mortality RR 0.85 (0.75 -- 0.97)0.97)

CaveatsCaveats

No MICU trialsNo MICU trials

The findings are driven by Van de The findings are driven by Van de

Bergh’s 2001 SICU study.Bergh’s 2001 SICU study.


We don’t really know any more about We don’t really know any more about

the value of tight glucose control.the value of tight glucose control.

Safety of electroconvulsive therapy in Safety of electroconvulsive therapy in patients receiving longpatients receiving long--term warfarin therapyterm warfarin therapy

•• Mehta V, Mueller PS, GonzalezMehta V, Mueller PS, Gonzalez--ArriazaArriaza HL, HL,

PankratzPankratz S, S, RummansRummans TA.TA.

•• Mayo Mayo ClinClin Proc. 2004 Nov 79(11):1396Proc. 2004 Nov 79(11):1396--14011401

•• Retrospective reviewRetrospective review

•• Jan 1994 Jan 1994 –– December 2001December 2001

Safety of ECT in patients receiving warfarinSafety of ECT in patients receiving warfarin

•• 35 patients on warfarin with therapeutic INR.35 patients on warfarin with therapeutic INR.

•• 17 A17 A--fib, 15 DVT, 10 PE, 8 CHF, 4 fib, 15 DVT, 10 PE, 8 CHF, 4 MechMech ValveValve

•• Received 300 Received 300 ECTsECTs; data available on 284.; data available on 284.

•• No bleeds.No bleeds.

•• 1 V1 V--tachtach admitted to ICU for monitoring.admitted to ICU for monitoring.


•• It is safe to continue warfarin, at It is safe to continue warfarin, at

therapeutic INR, through ECT.therapeutic INR, through ECT.

Association of risk of abnormal bleeding Association of risk of abnormal bleeding with degree of serotonin reuptake with degree of serotonin reuptake

inhibition by antidepressantsinhibition by antidepressants

•• MeijerMeijer WE, WE, HeerdinkHeerdink ER, Nolen WA, ER, Nolen WA, HeringsHerings

RM, RM, LeufkensLeufkens HG, HG, EgbertsEgberts ACAC

•• Arch Intern Med. 2004 Nov 22;164(21):2367Arch Intern Med. 2004 Nov 22;164(21):2367--7070

Association of SRI with bleedingAssociation of SRI with bleeding

•• Nested caseNested case--control studycontrol study

•• 64,000 new antidepressant users64,000 new antidepressant users

•• NetherlandsNetherlands

•• 19921992--20002000


•• CasesCases

•• all patients hospitalized for abnormal all patients hospitalized for abnormal

bleedingbleeding

•• ControlsControls

•• matched for age, sex, and date of inclusionmatched for age, sex, and date of inclusion

•• Classified degree of exposure to SRIClassified degree of exposure to SRI

•• High, Intermediate, LowHigh, Intermediate, Low


•• Logistic RegressionLogistic Regression

•• Adjusted for …Adjusted for …

•• History of hospitalization for bleeding.History of hospitalization for bleeding.

•• Medications:Medications:

•• aspirin, NSAIDs, anticoagulants, glucocorticoids, aspirin, NSAIDs, anticoagulants, glucocorticoids,

estrogens, progestins, H2 blockers, estrogens, progestins, H2 blockers, PPIsPPIs, ,

antidiabetic agentsantidiabetic agents


•• Abnormal BleedingAbnormal Bleeding

•• 47%47% UterineUterine

•• 16%16% Upper GIUpper GI

•• 11%11% CNSCNS

•• 26%26% Other*Other*

*epistaxis, hemoptysis, *epistaxis, hemoptysis,

hematoma, hematoma, surgicalsurgical, etc., etc.


•• Odds Ratio for abnormal bleeding by Odds Ratio for abnormal bleeding by

degree of exposure to SRI:degree of exposure to SRI:

•• High:High: 2.6 (1.4 2.6 (1.4 -- 4.8)4.8)

•• Intermediate: Intermediate: 1.9 (1.1 1.9 (1.1 -- 3.5)3.5)

•• Low:Low: 11

Association of Association of SSRIsSSRIs with bleedingwith bleeding•• High SRIHigh SRI

•• fluoxetine , clomipramine , paroxetine, sertralinefluoxetine , clomipramine , paroxetine, sertraline

•• Intermediate SRIIntermediate SRI

•• amitriptyline, citalopram, fluvoxamine, amitriptyline, citalopram, fluvoxamine,

imipramine, venlafaxineimipramine, venlafaxine

•• Low SRILow SRI

•• bupropion, desipramine, doxepin, mirtazapine, bupropion, desipramine, doxepin, mirtazapine,

nefazodone, nortriptyline, trazodonenefazodone, nortriptyline, trazodone


•• For procedures requiring punctilious hemostasis For procedures requiring punctilious hemostasis

considerconsider temporary discontinuation of potent temporary discontinuation of potent

SSRIsSSRIs in the immediate perioperative period.in the immediate perioperative period.

•• fluoxetine (Prozac), clomipramine (Anafranil), fluoxetine (Prozac), clomipramine (Anafranil),

paroxetine (Paxil), sertraline (Zoloft).paroxetine (Paxil), sertraline (Zoloft).

Antimicrobial prophylaxis for surgery: an Antimicrobial prophylaxis for surgery: an advisory statement from the National advisory statement from the National

Surgical Infection Prevention ProjectSurgical Infection Prevention Project

•• BratzlerBratzler DW and Houck PM for the groupDW and Houck PM for the group

•• ClinClin Infect Dis. 2004 Jun 15;38(12):1706Infect Dis. 2004 Jun 15;38(12):1706--1515

•• Goal: develop a consensus statement on Goal: develop a consensus statement on

surgical antimicrobial prophylaxis surgical antimicrobial prophylaxis

Antimicrobial prophylaxis for surgery Antimicrobial prophylaxis for surgery

advisory statement from the NSIPPadvisory statement from the NSIPP

•• Infusion of the first antimicrobial dose should Infusion of the first antimicrobial dose should

begin within 1 hour of the first surgical incision.begin within 1 hour of the first surgical incision.

•• Prophylactic antimicrobials should be stopped Prophylactic antimicrobials should be stopped

within 24 hours after the end of surgery.within 24 hours after the end of surgery.

•• Specific antimicrobials are appropriate for Specific antimicrobials are appropriate for

specific surgeries.specific surgeries.

Specific antimicrobials are Specific antimicrobials are appropriate for specific surgeriesappropriate for specific surgeries

•• CABG, Cardiothoracic (not transplant)CABG, Cardiothoracic (not transplant)

•• Vascular (AAA, arterial and vein bypass)Vascular (AAA, arterial and vein bypass)

•• ColorectalColorectal

•• Hip and Knee Arthroplasty (not revisions)Hip and Knee Arthroplasty (not revisions)

•• Hysterectomy (abdominal and vaginal)Hysterectomy (abdominal and vaginal)


•• There are now agreedThere are now agreed--upon upon

standards for the administration standards for the administration

of antimicrobial prophylaxis for of antimicrobial prophylaxis for

most major surgeries.most major surgeries.

Use of antimicrobial prophylaxis for major Use of antimicrobial prophylaxis for major

surgery: baseline results from the National surgery: baseline results from the National

Surgical Infection Prevention ProjectSurgical Infection Prevention Project

•• BratzlerBratzler DW, Houck PM, Richards C, DW, Houck PM, Richards C,

Steele L, Dellinger EP, Fry DE, Wright Steele L, Dellinger EP, Fry DE, Wright

C, Ma A, Carr K, Red LC, Ma A, Carr K, Red L

•• Arch Arch SurgSurg. 2005 Feb;140(2):174. 2005 Feb;140(2):174--82 82

Use of antimicrobial prophylaxis Use of antimicrobial prophylaxis for major surgeryfor major surgery

•• 2,965 acute2,965 acute--care US hospitals care US hospitals

•• 1 January 1 January -- 30 November 2001 30 November 2001

•• systematic, random sample ofsystematic, random sample of

•• 34,133 Medicare inpatients34,133 Medicare inpatients

Antimicrobial use in major surgeryAntimicrobial use in major surgery

•• In 56% antimicrobial was started within 1 In 56% antimicrobial was started within 1

hour before incision.hour before incision.

•• In 41% antimicrobials were discontinued In 41% antimicrobials were discontinued

within 24 hours after surgery.within 24 hours after surgery.

•• In 92% the antimicrobials used were In 92% the antimicrobials used were

consistent with published guidelines.consistent with published guidelines.


•• There are substantial opportunities There are substantial opportunities

to improve the use of perioperative to improve the use of perioperative

prophylactic antimicrobials.prophylactic antimicrobials.

SummarySummary

•• Future perioperative medicine research Future perioperative medicine research

should focus on interventions, not risk should focus on interventions, not risk

stratification.stratification.

•• The value of tight, perioperative The value of tight, perioperative

glucose control remains unverified.glucose control remains unverified.

SummarySummary

Continue warfarin through ECT (INR: 2Continue warfarin through ECT (INR: 2--3).3).

Consider holding potent Consider holding potent SSRIsSSRIs for surgeries for surgeries

requiring punctilious hemostasis.requiring punctilious hemostasis.

Encourage discontinuation of antimicrobials Encourage discontinuation of antimicrobials

within 24 hours after surgery.within 24 hours after surgery.

In search of fewer independent risk factorsIn search of fewer independent risk factors

•• BrotmanBrotman DJ, Walker E, DJ, Walker E,

Lauer MS, O'Brien RGLauer MS, O'Brien RG

•• Arch Intern Med. 2005 Jan Arch Intern Med. 2005 Jan

24;165(2):13824;165(2):138--4545


•• In the past 25 years the number of articles In the past 25 years the number of articles

published annually containing “independent risk published annually containing “independent risk

factor” or “independent predictor” in the title has factor” or “independent predictor” in the title has

gone from less than a handful to over 1200/year.gone from less than a handful to over 1200/year.

•• Many “risk factor” articles are about Many “risk factor” articles are about

perioperative risk.perioperative risk.


•• ““Independence” of a risk factor depends on Independence” of a risk factor depends on

the other risk factors included in the model.the other risk factors included in the model.

•• Can you really control for all risk factors? Can you really control for all risk factors?

No, for example, there are more than 110 No, for example, there are more than 110

“independent” risk factors for CAD.“independent” risk factors for CAD.


•• Reliance on statistical “significance” Reliance on statistical “significance”

without careful consideration of the without careful consideration of the

underlying pathophysiologic model can underlying pathophysiologic model can

lead to false conclusions.lead to false conclusions.


•• Consider reading this article to get a better Consider reading this article to get a better

understanding of risk factors understanding of risk factors -- independent independent

and nonand non--independent, causal and nonindependent, causal and non--causal, causal,

and of the distinction between therapeutic and of the distinction between therapeutic

targets and therapeutic markers.targets and therapeutic markers.

Documents

Update in Perioperative Medicine Electronic Handout - SGIMimpak.sgim.org/userfiles/file/AMHandouts/AM05/handouts/CU06.pdf · – Preop; postop days 1,3,7,d/c • CPK, ... • 35 periop