Excerise Tolerance and Post-Operative Outcomes in Patients with Pulmonary Hypertension (PHTN)

Self-Reported Exercise

Tolerance and

Perioperative Morbidity in

Pulmonary Hypertension

***July 2016 UPDATE***

Aalap C. Shah, MDClinical Fellow in Anesthesia

Boston Children’s HospitalHarvard Medical School

Pulmonary Hypertension (PHTN)◦ Progressive increase in mean pulmonary

arterial pressure (PAP) > 25 mmHg at rest;

◦ 30mmHg during exercise PAP > 30/15

Estimated PASP > 0.5 SBP

◦ Symptoms Dyspnea

Dizziness / Fatigue

Arrhythmias

Edema

Background

Pulmonary Hypertension (PHTN)

◦ Prevalence: 15-50 cases/1 million 1

◦ Incidence: 2.4 5-15 cases/1 million/year 1

◦ Average age: 53 +/- 14 yrs 1

◦ Overall survival: ~2.8 yrs (no treatment) 2

1 yr: 68%; 2 yr: 48%; 3 yr 34%

◦ Postoperative Mortality : 3.5-18%3-6

- Current risk stratification studies are underpowered (<100 patients)

- RCRI criteria analogue for PHTN patients?

Background

Pathogenesis

◦ Vasodilator/vasoconstrictorimbalance

PHTN Evaluation

Pre-Anesthesia Clinic (PAC) evaluation◦ Increasing chronic disease / comorbidity in

PHTN patients

◦ Increasing # of treatments / survival

◦ Expensive diagnostic and monitoring workup (+TTE)

◦ No consensus on severity assessment

PHTN: Outcomes Study

Retrospective chart review of all PHTN patients receiving elective procedures at UWMC (April 2007 – September 2013)

Outcome Measures

◦ LOS (< or ≥ 7 days)

◦ Mortality/Morbidity (< 30d after DOS)

◦ Hospital Readmissions

◦ Unplanned ICU Stay

Self-Reported Exercise Tolerance: Functional Status

During the pre-anesthesia clinic, all patients asked to estimate, without symptomatic limitation:

- # number of blocks they could walk- # flights of stairs they could climb

Functional Status (FS) < 4 METs -- Patients who could not walk 4 blocks or climb 2 flights of stairs.

Climbing 1 flight of stairs

1 metabolic equivalent of task (MET) = 3.5 ml O2/kg/min

Objective

Does self-reported functional status (FS) identify PHTN patients at risk for complications and increased hospital resource use?

“Can you climb 1 flight of stairs without getting short of breath?”

Data Collection / Selection

N=1922 N=661N=550 cases/370 patients

INCLUSION CRITERIA

1) PHTN diagnosis(ECHO or CATH)

2) ECHO data (<1 year prior to DOS)

3) elective non-CPB/non-OB procedures(GA or MAC)

EXCLUSION CRITERIA

1)Multiple procedure during the same hospital stay (n=43)

2) admissions >24h prior to surgery (n=34)

3) missing/incomplete FS data (n=31)

4) Procedure cx after induction (n=3)

Statistics

SPSS

◦ Χ2 statistic

◦ T-tests vs. Mann-Whitney U (ranked sums)

◦ Bivariate logistic regression (ENTER) -> OR, 95% CI

LOS

Morbidity/Mortality by discharge

Morbidity/Mortality by 30d

PHTN: Demographics vs LOS

Variables Overall

(N=550)

LOS £ 7

days

(N = 433)

LOS > 7

days

(N = 117)

P value

Male (%) 298 (54) 229 (53) 69 (59) .252

Age (years) 60 +/- 14 60 +/- 14 60 +/- 16 .850

Body Weight (kg) 91 +/- 34 92 +/- 33 89 +/- 34 .448 Height (cm) 170 +/- 10 170 +/- 10 171 +/- 10 .259

BMI (kg/m2) 32 +/- 12 32 +/- 12 31 +/- 12

.288

ASA Classification

II III IV

43 (8) 377 (69) 130 (24)

39 (9) 311(72) 83 (19)

4 (3) 66 (56) 47 (40)

.001

Poor Functional Status

< 4 METs (%)

273 (50) 197 (46) 76 (65) <.001

Variables Overall

(N=550) LOS £ 7

days

(N = 433)

LOS > 7

days

(N = 117)

P value

Hypertension (%) 365 (66) 298 (69) 67 (57) .021

Angina (%) 40 (7) 32 (7) 8 (7) 1.000

Coronary artery disease (%) 183 (34) 139 (32) 44 (38) .224

Congestive heart failure (%) 175 (32) 135 (31) 40 (34) .576

Arrhythmia (%) 245 (45) 191 (44) 54 (46) .753

VTE (%) 34 (6) 24 (6) 10 (9) .277

Asthma (%) 78 (14) 64 (15) 14 (12) .550

COPD (%) 74 (14) 53 (12) 21 (18) .125

Obstructive sleep apnea (%) 142 (26) 119 (28) 23 (20) .096

Diabetes (%) 156 (28) 130 (30) 26 (21) .106

Renal failure (%) 136 (25) 104 (24) 32 (27) .470

PAH medical therapy (%) 17 (3) 13 (3) 4 (3) .767

PHTN: Comorbidities vs. LOS

PHTN: Procedure/Echo vs. LOS

Variables Overall

(N=550) LOS £ 7

days

(N = 433)

LOS > 7

days

(N = 117)

P value

Number of procedures (n) 2 (2) 2 (2) 2 (2) .725

Most recent procedure (%) 370 (67) 298 (69) 72 (62) .149

Procedure Length (hours)

(mean +/- st. dev)*

1.9 +/- 1.9 1.6 +/- 1.4 3.0 +/- 2.8 <.001

Echocardiography finding

RAP ≥ 10mmHg** 169 (42) 130 (42) 39 (44) .716

PASP (mean, st. dev)*** 44 +/- 12 44 +/- 12 47 +/- 13 .035

Severe PHTN*** 50 (10) 37 (9) 13 (11) .470

Regression:Independent Associations

Variables Beta (SE) OR 95% CI P value

ASA Classification IV 1.09 (.24) 2.43 1.56-3.78 <.001

Open Surgical Approach .98 (.26) 2.67 1.60-4.44 <.001

Poor Functional Status

(< 4 METS)

.78 (.25) 2.19 1.35-3.56 .002

No systemic HTN .67 (.26) 1.94 1.18-3.20 .008

Preoperative PASP .01 (.01) 1.00 .99-1.02 .649

Procedure Length .36 (.07) 1.44 1.27-1.64 <.001

PHORS and Predicted LOS

1.8%

8.4%

18.0%

41.0%

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

35.0%

40.0%

45.0%

0 1 2 3+

Pro

ba

bil

ity

of

LO

s >

7 d

ay

s (%

)

PHORS Risk Score

ROC and PHORS Accuracy

Assessment of Multivariate Predictive model accuracy(a) Area Under Curve (AUC of 0.775 [95% CI: .728-.822])

(b) Adding echocardiogram variables such as PASP and RAP to the regression model did not significantly change the predictive value of the model

(PASP: 782 [95% CI: .735-.828]; RAP: .770 [95% CI: .715-.824])

PHORS and Outcomes

0.5%

15.6%

2.0%

14.0%

2.6%

30.4%

8.9%

17.4%

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0%

Mort

alit

y

An

y

Com

pli

cati

on

Un

pla

nned

IC

U

Ad

mis

sion

Rea

dm

issi

on

Prevalence (%)

PHORS ≥ 2

PHORS < 2p=.001

p=.102

p<.001

p=.336

Complications

10 deaths (mortality rate: 2.3%)

137 cases (complication rate: 25.0%)

35 unplanned ICU admissions (6.4%)

89 readmissions <30d (16.2%)

Complications PHORS < 2

(N = 200) PHORS ³ 2

(N = 350)

MI (%) 0 (0) 1 (0.3)

Cardiac Arrest (%) 0 (0) 2 (0.6)

CHF (%) 2 (1.0) 6 (1.7)

ARDS (%) 1 (0.5) 3 (0.9)

Respiratory Depression (%) 0 (0) 3 (0.9)

Reintubation (%) 1 (0.5) 6 (1.7)

Stroke/TIA (%) 1 (0.5) 0 (0)

VTE (%) 2 (1.0) 3 (0.9)

Arrhythmia (%) 7 (3.5) 21 (6.0)

Persistent Hypotension (%) 2 (1.0) 8 (2.3)

Acute renal failure (%) 3 (1.5) 9 (2.6)

Hemorrhage à tx or re-op (%) 2 (1.0) 6 (1.7)

Hematoma (%) 1 (0.5%) 1 (0.3)

Wound Debridement/Revision

(%)

1 (0.5) 8 (2.3)

Re-operation for bleeding (%) 1 (0.5) 4 (1.1)

Syncope (%) 1 (0.5) 2 (0.6)

Delirium (%) 4 (2.0) 13 (3.7)

PNA (%) 2 (1.0) 6 (1.7)

Sepsis (%) 3 (1.5) 2 (0.6)

UTI (%) 1 (0.5) 2 (0.6)

SSI (%) 1 (0.5) 2 (0.6)

Other abx 5 (2.5) 5 (1.4%)

Other 11 (5.5) 27 (7.7)

Limitations

Retrospective Study (Causation vs. Association)

Left-sided cardiac dysfunction patients included

Lacking non-PHTN case control group

◦ Outcome comparisons

◦ External Validity

Very few patients with severe PHTN More likely to experience severe outcomes

Conclusions

Poor functional status is an independent predictor of increased length of stay

Pre-operative echocardiogram (PASP and RAP) offers restricted additional prognostic value

Future Directions:◦ External Validation of Predictive Model vs non-

PHTN comparison◦ Interface with large data consortiums

National Registries Multicenter Perioperative Outcomes Group (MPOG)

◦ Cost analyses

Acknowledgements

• Gail Van Norman, MD – Professor and Director of Compliance

• G. Alec Rooke, MD, PhD – Professor• David Faraoni, MD – Research Assocaite

• Kevin Ma, BA – Clinical Research Coordinator

• Jessica Wang Olivia Wang Se Won An

• Edmond Lai Jacob DeBerry Daniel Masin

• Tammy Tarhini Shilpa Santhosh Ruby Chen

• Asha Melootu Jonathon Dang Zoe Ferguson-Steele

References1. Peacock AJ, Murphy NF, McMurray JJV, et al. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 2007 30:104-92. Badesch DB, Champion HC, Sanchez MA et al. “Diagnosis and assessment of pulmonary arterial hypertension”. J Am Coll Cardiol. 2009 Jun 30;54-563. Meyer S, McLaughlin VV, Seyfarth HJ, Bull TM, Vizza CD, Gomberg-Maitland M, Preston IR, Barberà JA, Hassoun PM, Halank M, Jaïs X, Nickel N, HoeperMM, Humbert M. Eur Respir J. 2013 Jun;41(6):1302-74. Ramakrishna G, Sprung J, Ravi BS, Chandrasekaran K, McGoon MD. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: predictors of perioperative morbidity and mortality. J Am Coll Cardiol. 2005 May 17;45(10):1691-9. 5. Minai OA, Venkateshiah SB, Arroliga AC. Surgical intervention in patients with moderate to severe pulmonary arterial hypertension. Conn Med 2006; 70: 239‐243.6. Price LC, Montani D, Jais X, Dick JR, Simonneau G, Sitbon O, Mercier FJ, Humbert M. Noncardiothoracic nonobstetric surgery in mild‐to‐moderate pulmonary hypertension. Eur Respir J 2010; 35: 1294‐1302.

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