Skip to main content
Top
Published in: Critical Care 2/2014

Open Access 01-04-2014 | Research

Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients?

Authors: Andrew JE Seely, Andrea Bravi, Christophe Herry, Geoffrey Green, André Longtin, Tim Ramsay, Dean Fergusson, Lauralyn McIntyre, Dalibor Kubelik, Donna E Maziak, Niall Ferguson, Samuel M Brown, Sangeeta Mehta, Claudio Martin, Gordon Rubenfeld, Frank J Jacono, Gari Clifford, Anna Fazekas, John Marshall

Published in: Critical Care | Issue 2/2014

Login to get access

Abstract

Introduction

Prolonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown.

Methods

We enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models.

Results

Of 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively.

Conclusions

Altered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability.

Trial registration

ClinicalTrials.gov NCT01237886. Registered 13 October 2010.
Appendix
Available only for authorised users
Literature
1.
go back to reference De Jonghe B, Bastuji-Garin S, Durand M-C, Malissin I, Rodrigues P, Cerf C, Outin H, Sharshar T: Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med 2007, 35: 2007-2015. 10.1097/01.ccm.0000281450.01881.d8CrossRefPubMed De Jonghe B, Bastuji-Garin S, Durand M-C, Malissin I, Rodrigues P, Cerf C, Outin H, Sharshar T: Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med 2007, 35: 2007-2015. 10.1097/01.ccm.0000281450.01881.d8CrossRefPubMed
2.
go back to reference Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH: Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002, 122: 2115-2121. 10.1378/chest.122.6.2115CrossRefPubMed Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH: Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002, 122: 2115-2121. 10.1378/chest.122.6.2115CrossRefPubMed
3.
go back to reference Rajakaruna C, Rogers CA, Angelini GD, Ascione R: Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg 2005, 130: 1270-1277. 10.1016/j.jtcvs.2005.06.050CrossRefPubMed Rajakaruna C, Rogers CA, Angelini GD, Ascione R: Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg 2005, 130: 1270-1277. 10.1016/j.jtcvs.2005.06.050CrossRefPubMed
4.
go back to reference Epstein SK, Ciubotaru RL, Wong JB: Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997, 112: 186-192. 10.1378/chest.112.1.186CrossRefPubMed Epstein SK, Ciubotaru RL, Wong JB: Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997, 112: 186-192. 10.1378/chest.112.1.186CrossRefPubMed
5.
go back to reference Esteban A, Frutos F, Tobin MJ, Alía I, Solsona JF, Valverdu V, Fernández R, de la Cal MA, Benito S, Tomás R, Carriedo D, Macías S, Blanco J: A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995, 332: 345-350. 10.1056/NEJM199502093320601CrossRefPubMed Esteban A, Frutos F, Tobin MJ, Alía I, Solsona JF, Valverdu V, Fernández R, de la Cal MA, Benito S, Tomás R, Carriedo D, Macías S, Blanco J: A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995, 332: 345-350. 10.1056/NEJM199502093320601CrossRefPubMed
6.
go back to reference Epstein SK: Predicting extubation failure: is it in (on) the cards? Chest J 2001, 120: 1061-1063.CrossRef Epstein SK: Predicting extubation failure: is it in (on) the cards? Chest J 2001, 120: 1061-1063.CrossRef
7.
go back to reference Epstein SK, Zilberberg MD, Jacoby C, Ciubotaru RL, Kaplan LM: Response to symptom-limited exercise in patients with the hepatopulmonary syndrome. Chest J 1998, 114: 736-741.CrossRef Epstein SK, Zilberberg MD, Jacoby C, Ciubotaru RL, Kaplan LM: Response to symptom-limited exercise in patients with the hepatopulmonary syndrome. Chest J 1998, 114: 736-741.CrossRef
8.
go back to reference Needham DM, Pronovost PJ: The importance of understanding the costs of critical care and mechanical ventilation. Crit Care Med 2005, 33: 1434-1435. 10.1097/01.CCM.0000166360.82336.75CrossRefPubMed Needham DM, Pronovost PJ: The importance of understanding the costs of critical care and mechanical ventilation. Crit Care Med 2005, 33: 1434-1435. 10.1097/01.CCM.0000166360.82336.75CrossRefPubMed
9.
go back to reference Dasta JF, McLaughlin TP, Mody SH, Piech CT: Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med 2005, 33: 1266-1271. 10.1097/01.CCM.0000164543.14619.00CrossRefPubMed Dasta JF, McLaughlin TP, Mody SH, Piech CT: Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med 2005, 33: 1266-1271. 10.1097/01.CCM.0000164543.14619.00CrossRefPubMed
10.
go back to reference Zeggwagh AA, Abouqal R, Madani N, Zekraoui A, Kerkeb O: Weaning from mechanical ventilation: a model for extubation. Intensive Care Med 1999, 25: 1077-1083. 10.1007/s001340051015CrossRefPubMed Zeggwagh AA, Abouqal R, Madani N, Zekraoui A, Kerkeb O: Weaning from mechanical ventilation: a model for extubation. Intensive Care Med 1999, 25: 1077-1083. 10.1007/s001340051015CrossRefPubMed
11.
go back to reference Yang KL, Tobin MJ: A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991, 324: 1445-1450. 10.1056/NEJM199105233242101CrossRefPubMed Yang KL, Tobin MJ: A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991, 324: 1445-1450. 10.1056/NEJM199105233242101CrossRefPubMed
12.
go back to reference Meade M, Guyatt G, Cook D, Griffith L, Sinuff T, Kergl C, Mancebo J, Esteban A, Epstein S: Predicting success in weaning from mechanical ventilation. Chest 2001, 120: 400S-424S. 10.1378/chest.120.6_suppl.400SCrossRefPubMed Meade M, Guyatt G, Cook D, Griffith L, Sinuff T, Kergl C, Mancebo J, Esteban A, Epstein S: Predicting success in weaning from mechanical ventilation. Chest 2001, 120: 400S-424S. 10.1378/chest.120.6_suppl.400SCrossRefPubMed
13.
go back to reference Frutos-Vivar F, Ferguson ND, Esteban A, Epstein SK, Arabi Y, Apezteguía C, González M, Hill NS, Nava S, D’Empaire G, Anzueto A: Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest J 2006, 130: 1664-1671.CrossRef Frutos-Vivar F, Ferguson ND, Esteban A, Epstein SK, Arabi Y, Apezteguía C, González M, Hill NS, Nava S, D’Empaire G, Anzueto A: Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest J 2006, 130: 1664-1671.CrossRef
14.
go back to reference MacIntyre N: Discontinuing mechanical ventilatory support. Chest 2007, 132: 1049-1056. 10.1378/chest.06-2862CrossRefPubMed MacIntyre N: Discontinuing mechanical ventilatory support. Chest 2007, 132: 1049-1056. 10.1378/chest.06-2862CrossRefPubMed
15.
go back to reference Esteban A, Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, Blanch L, Bonet A, Vazquez A, de Pablo R, Torres A, de la Cal MA, Macías S: Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Am J Respir Crit Care Med 1999, 159: 512-518. 10.1164/ajrccm.159.2.9803106CrossRefPubMed Esteban A, Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, Blanch L, Bonet A, Vazquez A, de Pablo R, Torres A, de la Cal MA, Macías S: Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Am J Respir Crit Care Med 1999, 159: 512-518. 10.1164/ajrccm.159.2.9803106CrossRefPubMed
16.
go back to reference Thille AW, Richard J-CM, Brochard L: The decision to extubate in the intensive care unit. Am J Respir Crit Care Med 2013, 187: 1294-1302. 10.1164/rccm.201208-1523CICrossRefPubMed Thille AW, Richard J-CM, Brochard L: The decision to extubate in the intensive care unit. Am J Respir Crit Care Med 2013, 187: 1294-1302. 10.1164/rccm.201208-1523CICrossRefPubMed
17.
go back to reference Bravi A, Longtin A, Seely AJE: Review and classification of variability analysis techniques with clinical applications. Biomed Eng Online 2011, 10: 1-27. 10.1186/1475-925X-10-1CrossRef Bravi A, Longtin A, Seely AJE: Review and classification of variability analysis techniques with clinical applications. Biomed Eng Online 2011, 10: 1-27. 10.1186/1475-925X-10-1CrossRef
18.
go back to reference Goldberger AL: Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside. Lancet 1996, 347: 1312-1314. 10.1016/S0140-6736(96)90948-4CrossRefPubMed Goldberger AL: Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside. Lancet 1996, 347: 1312-1314. 10.1016/S0140-6736(96)90948-4CrossRefPubMed
19.
go back to reference Goldberger AL: Heartbeats, hormones, and health: is variability the spice of life? Am J Respir Crit Care Med 2001, 163: 1289-1290. 10.1164/ajrccm.163.6.ed1801aCrossRefPubMed Goldberger AL: Heartbeats, hormones, and health: is variability the spice of life? Am J Respir Crit Care Med 2001, 163: 1289-1290. 10.1164/ajrccm.163.6.ed1801aCrossRefPubMed
20.
go back to reference Jacono FJ, Dick TE: Variability, measuring the spice of life. J Appl Physiol 2011, 111: 351-352. 10.1152/japplphysiol.00786.2011CrossRefPubMed Jacono FJ, Dick TE: Variability, measuring the spice of life. J Appl Physiol 2011, 111: 351-352. 10.1152/japplphysiol.00786.2011CrossRefPubMed
22.
go back to reference Buchan C, Bravi A, Seely A: Variability analysis and the diagnosis, management, and treatment of sepsis. Curr Infect Dis Rep 2012, 14: 512-521. 10.1007/s11908-012-0282-4CrossRefPubMed Buchan C, Bravi A, Seely A: Variability analysis and the diagnosis, management, and treatment of sepsis. Curr Infect Dis Rep 2012, 14: 512-521. 10.1007/s11908-012-0282-4CrossRefPubMed
23.
go back to reference Shen HN, Lin LY, Chen KY, Kuo PH, Yu CJ, Wu HD, Yang PC: Changes of heart rate variability during ventilator weaning. Chest 2003, 123: 1222-1228. 10.1378/chest.123.4.1222CrossRefPubMed Shen HN, Lin LY, Chen KY, Kuo PH, Yu CJ, Wu HD, Yang PC: Changes of heart rate variability during ventilator weaning. Chest 2003, 123: 1222-1228. 10.1378/chest.123.4.1222CrossRefPubMed
24.
go back to reference Bien MY, Hseu SS, Yien HW, Kuo BIT, Lin YT, Wang JH, Kou YR: Breathing pattern variability: a weaning predictor in postoperative patients recovering from systemic inflammatory response syndrome. Intensive Care Med 2004, 30: 241-247. 10.1007/s00134-003-2073-8CrossRefPubMed Bien MY, Hseu SS, Yien HW, Kuo BIT, Lin YT, Wang JH, Kou YR: Breathing pattern variability: a weaning predictor in postoperative patients recovering from systemic inflammatory response syndrome. Intensive Care Med 2004, 30: 241-247. 10.1007/s00134-003-2073-8CrossRefPubMed
25.
go back to reference Wysocki M, Cracco C, Teixeira A, Mercat A, Diehl J-L, Lefort Y, Derenne J-P, Similowski T: Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation. Crit Care Med 2006, 34: 2076-2083. 10.1097/01.CCM.0000227175.83575.E9CrossRefPubMed Wysocki M, Cracco C, Teixeira A, Mercat A, Diehl J-L, Lefort Y, Derenne J-P, Similowski T: Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation. Crit Care Med 2006, 34: 2076-2083. 10.1097/01.CCM.0000227175.83575.E9CrossRefPubMed
26.
go back to reference Hamilton PS, Tompkins WJ: Quantitative investigation of QRS detection rules using the MIT/BIH arrhythmia database. IEEE Trans Biomed Eng BME 1986, 33: 1157-1165.CrossRef Hamilton PS, Tompkins WJ: Quantitative investigation of QRS detection rules using the MIT/BIH arrhythmia database. IEEE Trans Biomed Eng BME 1986, 33: 1157-1165.CrossRef
27.
go back to reference Clifford GD, McSharry PE, Tarassenko L: Characterizing artefact in the normal human 24-hour RR time series to aid identification and artificial replication of circadian variations in human beat to beat heart rate using a simple threshold. Comput Cardiol 2002, 2002: 129-132.CrossRef Clifford GD, McSharry PE, Tarassenko L: Characterizing artefact in the normal human 24-hour RR time series to aid identification and artificial replication of circadian variations in human beat to beat heart rate using a simple threshold. Comput Cardiol 2002, 2002: 129-132.CrossRef
29.
go back to reference Li Q, Mark RG, Clifford GD: Robust heart rate estimation from multiple asynchronous noisy sources using signal quality indices and a Kalman filter. Physiol Meas 2007, 29: 15.PubMedCentralCrossRefPubMed Li Q, Mark RG, Clifford GD: Robust heart rate estimation from multiple asynchronous noisy sources using signal quality indices and a Kalman filter. Physiol Meas 2007, 29: 15.PubMedCentralCrossRefPubMed
30.
go back to reference Bhavani-Shankar K, Philip JH: Defining segments and phases of a time capnogram. Anesth Analg 2000, 91: 973-977. 10.1097/00000539-200010000-00038CrossRefPubMed Bhavani-Shankar K, Philip JH: Defining segments and phases of a time capnogram. Anesth Analg 2000, 91: 973-977. 10.1097/00000539-200010000-00038CrossRefPubMed
31.
go back to reference Pounds S, Cheng C: Robust estimation of the false discovery rate. Bioinformatics 2006, 22: 1979-1987. 10.1093/bioinformatics/btl328CrossRefPubMed Pounds S, Cheng C: Robust estimation of the false discovery rate. Bioinformatics 2006, 22: 1979-1987. 10.1093/bioinformatics/btl328CrossRefPubMed
32.
go back to reference Polikar R: Ensemble based systems in decision making. IEEE Circ Syst Mag 2006, 6: 21-45.CrossRef Polikar R: Ensemble based systems in decision making. IEEE Circ Syst Mag 2006, 6: 21-45.CrossRef
33.
go back to reference Hastie T, Tibshirani R, Friedman JJH: The elements of statistical learning. Volume 1. New York: Springer; Hastie T, Tibshirani R, Friedman JJH: The elements of statistical learning. Volume 1. New York: Springer;
34.
go back to reference Boles J-M, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A: Weaning from mechanical ventilation. Eur Respir J 2007, 29: 1033-1056. 10.1183/09031936.00010206CrossRefPubMed Boles J-M, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A: Weaning from mechanical ventilation. Eur Respir J 2007, 29: 1033-1056. 10.1183/09031936.00010206CrossRefPubMed
35.
go back to reference Mehta S, Nelson DL, Klinger JR, Buczko GB, Levy MM: Prediction of post-extubation work of breathing. Crit Care Med 2000, 28: 1341-1346. 10.1097/00003246-200005000-00014CrossRefPubMed Mehta S, Nelson DL, Klinger JR, Buczko GB, Levy MM: Prediction of post-extubation work of breathing. Crit Care Med 2000, 28: 1341-1346. 10.1097/00003246-200005000-00014CrossRefPubMed
36.
go back to reference El-Khatib M, Jamaleddine G, Soubra R, Muallem M: Pattern of spontaneous breathing: potential marker for weaning outcome. Spontaneous breathing pattern and weaning from mechanical ventilation. Intensive Care Med 2001, 27: 52-58. 10.1007/s001340000758CrossRefPubMed El-Khatib M, Jamaleddine G, Soubra R, Muallem M: Pattern of spontaneous breathing: potential marker for weaning outcome. Spontaneous breathing pattern and weaning from mechanical ventilation. Intensive Care Med 2001, 27: 52-58. 10.1007/s001340000758CrossRefPubMed
37.
go back to reference Papaioannou VE, Chouvarda I, Maglaveras N, Dragoumanis C, Pneumatikos I: Changes of heart and respiratory rate dynamics during weaning from mechanical ventilation: A study of physiologic complexity in surgical critically ill patients. J Crit Care 2011, 26: 262-272. 10.1016/j.jcrc.2010.07.010CrossRefPubMed Papaioannou VE, Chouvarda I, Maglaveras N, Dragoumanis C, Pneumatikos I: Changes of heart and respiratory rate dynamics during weaning from mechanical ventilation: A study of physiologic complexity in surgical critically ill patients. J Crit Care 2011, 26: 262-272. 10.1016/j.jcrc.2010.07.010CrossRefPubMed
38.
go back to reference Arcentales A, Giraldo BF, Caminal P, Benito S, Voss A: Recurrence quantification analysis of heart rate variability and respiratory flow series in patients on weaning trials. 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2011, 2724-2727.CrossRef Arcentales A, Giraldo BF, Caminal P, Benito S, Voss A: Recurrence quantification analysis of heart rate variability and respiratory flow series in patients on weaning trials. 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2011, 2724-2727.CrossRef
39.
go back to reference Clifford GD: ECG statistics, noise, artifacts, and missing data. In Advanced Methods and Tools for ECG Analysis. Edited by: Clifford DG, Azuaje F, McSharry PE. Boston/London: Artech House Publishing; 2006:55-99. Clifford GD: ECG statistics, noise, artifacts, and missing data. In Advanced Methods and Tools for ECG Analysis. Edited by: Clifford DG, Azuaje F, McSharry PE. Boston/London: Artech House Publishing; 2006:55-99.
40.
go back to reference Clifford GD, Behar J, Li Q, Rezek I: Signal quality indices and data fusion for determining clinical acceptability of electrocardiograms. Physiol Meas 2012, 33: 1419-1433. 10.1088/0967-3334/33/9/1419CrossRefPubMed Clifford GD, Behar J, Li Q, Rezek I: Signal quality indices and data fusion for determining clinical acceptability of electrocardiograms. Physiol Meas 2012, 33: 1419-1433. 10.1088/0967-3334/33/9/1419CrossRefPubMed
41.
go back to reference Bien MY, Lin YS, Shih CH, Yang YL, Lin HW, Bai KJ, Wang JH, Kou YR: Comparisons of predictive performance of breathing pattern variability measured during T-piece, automatic tube compensation, and pressure support ventilation for weaning intensive care unit patients from mechanical ventilation. Crit Care Med 2011, 39: 2253-2262. 10.1097/CCM.0b013e31822279edCrossRefPubMed Bien MY, Lin YS, Shih CH, Yang YL, Lin HW, Bai KJ, Wang JH, Kou YR: Comparisons of predictive performance of breathing pattern variability measured during T-piece, automatic tube compensation, and pressure support ventilation for weaning intensive care unit patients from mechanical ventilation. Crit Care Med 2011, 39: 2253-2262. 10.1097/CCM.0b013e31822279edCrossRefPubMed
Metadata
Title
Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients?
Authors
Andrew JE Seely
Andrea Bravi
Christophe Herry
Geoffrey Green
André Longtin
Tim Ramsay
Dean Fergusson
Lauralyn McIntyre
Dalibor Kubelik
Donna E Maziak
Niall Ferguson
Samuel M Brown
Sangeeta Mehta
Claudio Martin
Gordon Rubenfeld
Frank J Jacono
Gari Clifford
Anna Fazekas
John Marshall
Publication date
01-04-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13822

Other articles of this Issue 2/2014

Critical Care 2/2014 Go to the issue