Skip to main content
SpringerLink
Log in

Autonomic regulation during mild therapeutic hypothermia in cardiopulmonary resuscitated patients

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Objective

We investigated whether there are differences in autonomic cardiovascular regulation in resuscitated patients undergoing therapeutic hypothermia (TH) in relation to the clinical outcome.

Method

Between 2005 and 2007, 18 consecutive resuscitated patients were enrolled. ECG and blood pressure data were recorded for 48 h during hypothermia and warming up to a body core temperature of 36°C. Autonomic regulation was assessed by applying time, frequency, and non-linear dynamics domain methods from heart rate and blood pressure variability (HRV/BPV) analyses.

Results

Nine patients survived with good neurological recovery, and nine patients died during the ICU stay. In both groups, we found a decreased HRV presented by standard deviation of R–R intervals (sdNN) below 50 ms2 at each time of measurement. Immediately after recovery to a body core temperature of 36°C, a significant higher HRV was found in survivors compared to non-survivors by means of indices sdNN (40.2 ± 19.5 vs. 10.9 ± 4.1 ms2, P = 0.01), R–R intervals distribution histogram [shannon] (3.7 ± 0.6 vs. 2.2 ± 0.4, P = 0.008), very low frequency band [VLF] (152.2 ± 99.3 vs. 3.4 ± 1.9, P = 0.001) and the variance of the time series of R–R intervals [Wsdvar] (1.16 ± 0.52 vs. 0.29 ± 0.25, P = 0.02) . A decreased spontaneous BPV was found only among survivors comparing blood pressure characteristics within stable hypothermia to the initial state before hypothermia.

Conclusion

Resuscitated patients show a significantly reduced HRV before, during and after TH. Compared to survivors, the non-survivors show a further and significantly decrease of HRV immediately after hypothermia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AMI:

Acute myocardial infarction

CPR:

Cardiopulmonary resuscitation

ECG:

Electrocardiogram

GOS:

Glasgow Outcome Score

HRV/BPV:

Heart rate variability/blood pressure variability

sdNN:

Standard deviation of R–R intervals

VF:

Ventricular fibrillation

VLF:

Spectral power in the very low frequency band

Wsdvar:

Standard deviation of word sequence

Plvar:

Probability of low variance HRV pattern

Shannon:

Shannon entropy of the R–R intervals distribution histogram

NSE:

Neuron-specific Enolase

References

  1. de Vreede-Swagemakers JJ, Gorgels AP, Dubois-Arbouw WI (1997) Out-of-hospital cardiac arrest in the 1990s: a population-based study in the Maastrich area on incidence, characteristics and survival. J Am Coll Cardiol 30:1500–1505

    Article  PubMed  Google Scholar 

  2. Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, Perkins GD (2010) European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 81:1305–1352

    Article  PubMed  Google Scholar 

  3. Hypothermia after Cardiac Arrest Study Group (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346(8):549–556

    Article  Google Scholar 

  4. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346(8):557–563

    Article  PubMed  Google Scholar 

  5. Wolfrum S, Radke PW, Pischon T, Willich SN, Schunkert H, Kurowski V (2007) Mild therapeutic hypothermia after cardiac arrest—a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units. Resuscitation 72:207–213

    Article  PubMed  Google Scholar 

  6. Storm C, Schefold JC, Kerner T, Schmidbauer W, Gloza J, Krueger A, Jörres A, Hasper D (2008) Prehospital cooling with hypothermia caps (PreCoCa): a feasibility study. Clin Res Cardiol 97:768–772

    Article  PubMed  Google Scholar 

  7. Cabanas JG, Brice JH, De Maio VJ, Meyers B, Hinchey PR (2010) Field-induced therapeutic hypothermia for neuroprotection after out-of hospital cardiac arrest: a systemic review of the literature. J Emerg Med

  8. Simon T, Becker R, Voss F, Bikou O, Hauck M, Licka M, Katus HA, Bauer A (2008) Elevated B-type natriuretic peptide levels in patients with nonischemic cardiomyopathy predict occurrence of arrhytmic events. Clin Res Cardiol 97:306–309

    Article  PubMed  CAS  Google Scholar 

  9. Peter JG, Glos M, Blau A, Penzel Tbaumann G, Fietze I (2010) Daytime baroreflex sensitivity in patients with primary insomnia. Clin Res Cardiol 99

  10. von Känel R, Carney RM, Thao S, Whooley MA (2010) Heart rate variability ans biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul study. Clin Res Cardiol 99

  11. Kaya EB, Okutucu S, Aksoy H, Karakulak UN, Tulumen E, Ozdemir O, Inanici F, Aytemir K, Kabakci G, Tokgozoglu L, Ozkutlu H, Oto A (2010) Evaluation of cardiac autonomic function in patients with ankylosing sponylitis via heart rate recovery and heart rate variability. Clin Res Cardiol 99:803–808

    Article  PubMed  Google Scholar 

  12. Buob A, Winter H, Kindermann M, Becker G, Möller JC, Oertel WH, Böhm M (2010) Parasympathetic but not sympathetic cardiac dysfunction at early stages of Parkinson’s disease. Clin Res Cardiol 99:701–706

    Article  PubMed  Google Scholar 

  13. Hohnloser SH, Klingenheben T (1996) Stratification of patients at risk for sudden cardiac death with special reference to the autonomic nervous system. Z Kardiol 85:35–43

    PubMed  Google Scholar 

  14. Klingenheben T, Rapp U, Hohnloser SH (1995) Circadian variation of heart rate variability in postinfarction patients with and without life-threatening ventricular tachyarrhythmias. J Cardiovasc Electrophysiol 6:357–364

    Article  PubMed  CAS  Google Scholar 

  15. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351:478–484

    Article  PubMed  CAS  Google Scholar 

  16. Klingenleben T, Zabel M, Hohnloser SH (1998) Kurzzeitanalyse der Herzfrequenz-variabilität im Zeitbereich zur Prognosebeurteilung nach Myokardinfarkt: methodologisch sinnvolle Alternative zum Langzeit-EKG? Z Kardiol 87:128–133

    Article  Google Scholar 

  17. Przibille O, Liebrich A, Nowak B, Rosocha S, Zellerhoff Ch, Geil S, Himmrich E, Treese N, Meyer J (1998) Die prognostische Bedeutung der Herzfrequenzvariabilitätsanalyse bei Patienten mit dilatativer Kardiomyopathie. Z Kardiol 87:453–458

    Article  PubMed  CAS  Google Scholar 

  18. Kurths J, Voss A, Saparin P, Witt A, Kleiner HJ, Wessel N (1995) Quantitative analysis of heart rate variability. Chaos 5:88–94

    Article  PubMed  Google Scholar 

  19. Smilde TD, van Veldhuisen DJ, van den Berg MP (2009) Prognostic value of heart rate variability and ventricular arrhythmias during 13-year follow up in patients with mild to moderate heart failure. Clin Res Cardiol 98:233–239

    Article  PubMed  CAS  Google Scholar 

  20. Anderson F, Schlattmann P, Roll S, Müller-Riemenschneider F, Binting S, Willich SN (2010) Regional variation of mortality from ischemic heart disease in Germany from 1998 to 2007. Clin Res Cardiol 99:511–518

    Article  Google Scholar 

  21. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation 93:1043–1065

    Article  Google Scholar 

  22. Voss A, Schulz S, Schroeder R, Baumert M, Caminal P (2009) Methods derived from non-linear dynamics for analysing heart rate variability. Philos Transact A Math Phys Eng Sci 367:277–296

    Article  PubMed  Google Scholar 

  23. Sleight P, La Rovere MT, Mortara A, Pinna G, Maestri R, Leuzzi S, Bianchini B, Tavazzi L, Bernardi L (1995) Physiology and pathophysiology of heart rate and blood pressure variability in humans: is power spectral analysis largely an index of baroreflex gain? Clin Sci (Lond) 88:103–109

    CAS  Google Scholar 

  24. Leder U, Pohl HP, Baier V, Baumert M, Liehr M, Haueisen J, Voss A, Figulla HR (2002) Alternans of blood pressure and heart rate in dilated cardiomyopathy. Pacing Clin Electrophysiol 25:1307–1314

    Article  PubMed  Google Scholar 

  25. Truebner S, Cygankiewicz I, Schroeder R, Baumert M, Vallverdú M, Caminal P, Vazquez R, Bayés de Luna A, Voss A (2006) Compression entropy contributes to risk stratification in patients with cardiomyopathy. Biomed Tech 51:77–82

    Article  Google Scholar 

  26. Voss A, Kurths J, Kleiner HJ, Witt A, Wessel N, Saparin P, Osterziel KJ, Schurath R, Dietz R (1996) The application of methods of non-linear dynamics for the improved and predictive recognition of patients threatened by sudden cardiac death. Cardiovasc Res 31:419–433

    PubMed  CAS  Google Scholar 

  27. Chernow B, Lake CR, Zaritsky A, Finton CK, Casey L, Rainey TG, Fletcher JR (1983) Sympathetic nervous system „switch off” with severe hypothermia. Crit Care Med 11:677–680

    Article  PubMed  CAS  Google Scholar 

  28. Jacobshagen C, Pelster T, Pax A, Horn W, Schmidt-Schweda S, Unsöld BW, Seidler T, Hasenfuss G, Maier LS (2010) Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing myocardium. Clin Res Cardiol 99:267–276

    Article  PubMed  Google Scholar 

  29. Hsu CY, Huang CH, Chang WT, Chen HW, Cheng HJ, Tsai MS, Wang TD, Yen ZS, Lee CC, Chen SC, Chen WJ (2009) Cardioprotective effect of therapeutic hypothermia for post-resuscitation dysfunction. Shock 32:210–216

    Article  PubMed  Google Scholar 

  30. Cook S, Togni M, Schaub MC et al (2006) High heart rate: a cardivascular risk factor? Eur Heart J 27:2387–2393

    Article  PubMed  Google Scholar 

  31. Böhm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brahme A, Lerebours G, Tavazzi L, (SHIFT Investigators) (2010) Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet 376:886–894

    Article  PubMed  Google Scholar 

  32. Tiainen M (2009) Arrhythmias and heart rate variability during and after therapeutic hypothermia for cardiac arrest. Crit Care Med 37:403–409

    Article  PubMed  Google Scholar 

  33. Sabharwal R, Coote JH, Johns EJ, Egginton S (2004) Effect of hypothermia on baroreflex control of heart rate and renal sympathetic nerve activity in anaesthetized rats. J Physiol 557:247–259

    Article  PubMed  CAS  Google Scholar 

  34. Tanaka M, Nagasaki G, Nishikawa T (2001) Moderate hypothermia depresses arterial baroreflex control of heart rate during, and delays its recovery after, general anesthesia in humans. Anesthesiology 95:51–55

    Article  PubMed  CAS  Google Scholar 

  35. La Rovere MT, Pinna GD, Hohnloser SH, Marcus FI, Mortara A, Nohara R, Bigger JT Jr, Camm AJ, Schwartz PJ, ATRAMI Investigators (2001) Autonomic Tone and Reflexes after Myocardial Infarction: Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials. Circulation 103:2072–2077

    PubMed  CAS  Google Scholar 

  36. La Rovere MT (2000) Baroreflex sensitivity as a new marker for risk stratification. Z Kardiol 89:III/44–III/50

    Google Scholar 

  37. De Ferrari GM, Sanzo A, Bertoletti A, Specchia G, Vanoli E, Schwartz PJ (2007) Baroreflex sensitivity predicts long-term cardiovascular mortality after myocardial infarction even in patients with preserved left ventricular function. J Am Coll Cardiol 50:2285–2290

    Article  PubMed  Google Scholar 

  38. Hohnloser SH, Klingenheben T, van de Loo A, Hablawetz E, Just H, Schwartz PJ (1994) Reflex versus tonic vagal activity as a prognostic parameter in patients with sustained ventricular tachycardia or ventricular fibrillation. Circulation 89:1068–1073

    PubMed  CAS  Google Scholar 

  39. Klingenheben T, Credner S, Grönefeld G, Zabel M, Li Y, Hohnloser SH (1999) Kardialer autonomer Tonus zur Risikostratifikation nach Myokardinfarkt: Ergebnisse einer prospektiven Langzeitstudie bei 411 konsekutiven Patienten. Z Kardiol 88:400–409

    Article  PubMed  CAS  Google Scholar 

  40. Zandbergen EG, Hijdra A, Koelman JH, PROPAC Study Group et al (2006) Prediction of poor outcome within the first 3 days of post-anoxic coma. Neurology 66:62–68

    Article  PubMed  CAS  Google Scholar 

  41. Pfeifer R, Börner A, Krack A et al (2005) Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale. Resuscitation 65:49–55

    Article  PubMed  CAS  Google Scholar 

  42. Schmidt H, Müller-Werdan U, Hoffmann T, Francis DP, Piepoli MF, Rauchhaus M, Prondzinsky R, Loppnow H, Buerke M, Hoyer D, Werdan K (2005) Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med 33:1994–2002

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author`s contributions

All authors participated in the design and coordination of the study and draft of the manuscript. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany

    R. Pfeifer, C. Ehrhardt & H. R. Figulla

  2. Department of Medical Engineering and Biotechnology, University of Applied Sciences Jena, Carl-Zeiss-Promenade 2, 07745, Jena, Germany

    J. Hopfe & A. Voss

  3. Department of Geriatrics, University Hospital Jena, Bachstrasse 18, 07740, Jena, Germany

    M. Goernig

Authors
  1. R. Pfeifer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Hopfe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Ehrhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Goernig
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. R. Figulla
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Voss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to R. Pfeifer or A. Voss.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pfeifer, R., Hopfe, J., Ehrhardt, C. et al. Autonomic regulation during mild therapeutic hypothermia in cardiopulmonary resuscitated patients. Clin Res Cardiol 100, 797–805 (2011). https://doi.org/10.1007/s00392-011-0314-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-011-0314-3

Keywords

Search

Navigation