Article

The interplay between autonomic imbalance, cardiac dysfunction, and blood pressure variability in sepsis

322 Correspondence / American Journal of Emergency Medicine 36 (2018) 319338

https://doi.org/10.1016/j.ajem.2017.11.045

References

  1. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Bio- metrics 1988;44:837-45.
  2. Harrell FE. Regression modeling Strategies: with applications to linear, logistic regres- sion, and survival analysis. New York: Springer-Verlag; 2001.
  3. Neter J, Kutner M, Nachtsheim C, Wasserman W. Applied linear statistical models. 4th ed. McGraw-Hill; Irwin; 1996.
  4. Multicollinearity. Available at http://www.public.iastate.edu/~alicia/stat328/Model% 20diagnostics.pdf, Accessed date: 11 November 2017.
  5. Multicollinearity. Available at http://people.stat.sc.edu/hansont/stat704/vif_704.pdf, Accessed date: 11 November 2017.

Autonomic imbalance in sepsis

We read with great interest the article by Nouriel et al. in the American Journal of Emergency Medicine [1]. The authors found a pos- itive correlation between Blood pressure variability and both lactate levels and Sequential Organ Failure Assessment scores. The role of the autonomic nervous system has been increasingly studied in patients with sepsis. Recent studies have shown that glycaemic variabil- ity [2], heart rate variability [3] and systolic blood pressure variability [4] is associated with prognosis in septic patients. Heart rate and blood pressure variability exhibits complex patterns that may give insight into the interdependence of the autonomic nervous system and inflam- mation in sepsis.

cardiac dysfunction plays a key role in the pathology and prognosis of septic shock. Sepsis-induced cardiomyopathy is a systolic and diastol- ic dysfunction of both the left and right ventricles of the heart [5]. Natri- uretic peptides and cardiac troponins have emerged as potential candidates for the evaluation and quantification of cardiac function and for risk stratification in patients with sepsis [5]. Therefore, we think that association between biomarkers of myocardial injury/cardiac dysfunction and blood pressure variability should be evaluated by the authors.

Funda Sungur Biteker, MD

Yatagan State Hospital, Department of Infectious Diseases and Clinical

Microbiology, Turkey

Bulent Ozlek, MD* Oguzhan Celik, MD Eda Ozlek, MD Cem Cil, MD

Volkan Dogan, MD, Assistant Prof Murat Biteker, MD, Assistant Prof

Mugla University, Faculty of Medicine, Department of Cardiology, Turkey

*Corresponding author at: Mugla Sitki Kocman Universitesi Tip Fakultesi, Orhaniye Mah. Haluk Ozsoy Cad., 48000/Mugla, Turkey. E-mail address: [email protected] (B. Ozlek)

16 October 2017

https://doi.org/10.1016/j.ajem.2017.11.054

References

  1. Nouriel JE, Millis SR, Ottolini J, Wilburn JM, Sherwin RL, Paxton JH. Blood pressure var- iability as an indicator of sepsis severity in adult emergency department patients. Am J Emerg Med 2017 Sep 14 pii: S0735-6757(17)30742-8 https://doi.org/10.1016/j. ajem.2017.09.017. (in press).
  2. Silveira LM, Basile-Filho A, Nicolini EA, Dessotte CAM, Aguiar GCS, Stabile AM. Glycaemic variability in patients with severe sepsis or septic shock admitted to an In- tensive Care Unit. Intensive Crit Care Nurs 2017 Aug;41:98-103. https://doi.org/10. 1016/j.iccn.2017.01.004 [Epub 2017 Mar 18].
  3. de Castilho FM, Ribeiro ALP, da Silva JLP, Nobre V, de Sousa MR. Heart rate variability as predictor of mortality in sepsis: a prospective cohort study. PLoS One 2017 Jun 27; 12(6):e0180060. https://doi.org/10.1371/journal.pone.0180060 eCollection 2017.
  4. Tang Y, Sorenson J, Lanspa M, Grissom CK, Mathews VJ, Brown SM. Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study. BMC Anesthesiol 2017 Jun 17;17(1):82. https://doi.org/10.1186/ s12871-017-0377-4.
  5. Klouche K, Pommet S, Amigues L, Bargnoux AS, Dupuy AM, Machado S, et al. Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: rela- tionships with systolic myocardial dysfunction and intensive care unit mortality. J In- tensive Care Med 2014 Jul-Aug;29(4):229-37.

The interplay between autonomic imbalance, cardiac dysfunction, and blood pressure variability in sepsis

Thank you for your interest in our study, and for the opportunity to elaborate further on our investigation into the inter-relationship be- tween the autonomic nervous system (ANS), heart, and peripheral vas- culature in the septic patient. Patients with sepsis are at risk for cardiac dysfunction, often associated with elevated serum troponin levels, which have been validated as independent predictors of mortality in sepsis [1-3]. In a meta-analysis of studies published between 1998 and 2012, 60.5% of the 1857 septic patients had an elevated troponins [4]. El- evated troponin levels are a consequence of cardiac injury. Identifica- tion of a noninvasive, readily available hemodynamic marker that could suggest the presence of impending myocardial injury in sepsis could have implications for the prevention or mitigation of myocardial injury. Although the relationship between Autonomic dysfunction, as reflected in part by blood pressure variability , and cardiac dys- function is not yet well-delineated, we feel that this area of research has the potential to impact sepsis management, especially as it relates to the reduction of the morbidity and mortality associated with septic cardiomyopathy.

The etiology of cardiac dysfunction in sepsis is most likely multifac- torial [5-6]. Uncoupling between the ANS and the cardiovascular system in sepsis has been previously described [7]. The ANS can affect the heart via both direct innervation and indirectly via decreased perfusion sec- ondary to pathologic alterations in blood pressure regulation. heart rate variability has previously been shown to be a non-invasive, albeit indirect, measure of ANS dysfunction [8]. We believe that incor- porating BPV with HRV as an assessment of illness severity may lead to improved hemodynamic monitoring in sepsis. The precise relation- ship between Autonomic instability and septic cardiomyopathy is un- clear. The direction of the variation in heart rate may be different from the direction of the variation of blood pressure: severe illness may be as- sociated with a low HRV and a high BPV [9-14]. Accounting for the pre- cise nature of these differences in future studies will be challenging.

In addition to altered autonomic function in sepsis, autoregulation and the microcirculation may similarly be altered in sepsis [15]. Auto- regulation functions independent of the autonomic nervous system, and plays a significant role in cerebral and renal perfusion. Labile blood pressures arguably could stress an impaired auto-regulatory sys- tem. Autonomic nuclei within the brain are dependent upon adequate cerebral perfusion. Malperfusion of the autonomic centers could con- ceptually contribute to cardiac dysfunction in sepsis. Acute kidney inju- ry is another common sequela of sepsis [16]. Cardio-renal syndrome, where primary dysfunction of either the heart or the kidneys results in a secondary dysfunction to the other organ, is an emerging area of study, and sepsis appears to be an important cause of this condition [17]. Thus, in addition to evaluating the association between markers of myocardial injury and BPV, evaluating the association between markers of kidney injury and BPV may demonstrate clinical utility. Where BPV fits within the complex interrelationship between the brain, heart and kidneys remains to be determined.

Correspondence / American Journal of Emergency Medicine 36 (2018) 319338 323

Despite aggressive management, mortality from sepsis remains high [18]. However, we know that early clinical intervention is associated with improved clinical outcomes [19]. Tools to aid in the identification for the need for early clinical intervention are needed to mitigate the high mortality commonly seen in sepsis. Your proposal for an evaluation of the association between markers of cardiac dysfunction and BPV offers the possibility of formulating such tools. Although our accompanying manuscript offers a brief glimpse into cardiovascular changes experi- enced by a small cohort of observed patients suffering from sepsis, we feel that larger studies of this effect are both warranted and important to establishing a greater understanding of the relationship between ANS dysfunction and myocardial injury in sepsis. Our group does intend to pursue a greater understanding of this relationship, and your query does underscore the need for this line of investigation. It is our aim that clarifying the relationship between BPV, HRV and myocardial injury will help providers detect and intervene upon septic myocardial dysfunction earlier in sepsis management, hopefully resulting in better long-term out- comes for our patients. Although this is a nascent line of investigation, we feel that it may hold the potential for significant advances in the treat- ment of this heterogeneous yet highly lethal condition.

Jacob E. Nouriel, BA* James H. Paxton, MD, MBA

Department of Emergency Medicine, Wayne State University School of

Medicine, Detroit, MI, USA

*Corresponding author at: Wayne State University School of Medicine,

540 E. Canfield St., Detroit, MI 48201, USA.

E-mail address: [email protected] (J.E. Nouriel)

17 November 2017

https://doi.org/10.1016/j.ajem.2017.11.055

References

  1. Pulido JN, Afessa B, Masaki M, et al. Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock. Mayo Clin Proc 2012; 87(7):620-8.
  2. Landesberg G, Jaffe As, Gilon D, et al. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilata- tion. Crit Care Med 2014;42(4):790-800.
  3. Bessiere F, Khenifer S, Dubourg J, Durieu I, Lega JC. Prognostic value of troponins in

sepsis: a meta-analysis. Intensive Care Med 2013;39(7):1181-9.

  1. Sheyin O, Davies O, Duan W, et al. The prognostic significance of troponin elevation in patients with sepsis: a meta-analysis. Heart Lung 2015;44:75-81.
  2. Sato R, Nasu M. A review of sepsis-induced cardiomyopathy. J Intensive Care 2015;3:

48.

  1. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med 2007;35(6):1599-608.
  2. Toweill DL, Sonnenthal K, Kimberly B, et al. Linear and nonlinear analysis of hemodynamic signals during sepsis and septic shock. Crit Care Med 2000;28(6): 2051-7.
  3. Heart rate variability: standards of measurement, physiological interpretation and clinical use Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, Circulation 1996;93(5):1043-65.
  4. de Castilho FM, ALP Ribeiro, da Silva JLP, Nobre V, de Sousa MR. Heart rate variability as predictor of mortality in sepsis: a prospective cohort study. PLoS One 2017 Jun 27; 12(6):e0180060.
  5. Barnaby D, Ferrick K, Kaplan DT, et al. Heart rate variability in emergency depart- ment patients with sepsis. Acad Emerg Med 2002;9(7):661-70.
  6. Pontet J, Contreras P, Curbelo A, et al. Heart rate variability as early marker of mul-

tiple organ dysfunction syndrome in septic patients. J Crit Care 2003;18(3):156-63.

  1. Pandey NR, Bian Y, Shou S. Significance of blood pressure variability in patients with sepsis. World J Emerg Med 2014;5(1):42-7.
  2. Tang Y, Sorenson J, Lanspa M, CK Grissom, Mathews VJ, SM Brown. Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospec- tive cohort study. BMC Anesthesiol 2017 Jun 17;17(1):82.
  3. Je Nouriel, Sr Millis, Ottolini J, Jm Wilburn, Rl Sherwin, Paxton JH. Blood pressure var- iability as an indicator sepsis severity in adult emergency department patients. Am J Emerg Med 2017. https://doi.org/10.1016/j.ajem.2017.09.017.
  4. Hernandez G, Bruhn A, Ince C. Microcirculation in sepsis: new perspectives. Curr Vasc Pharmacolo 2013;11(2):161-9.
  5. Bagshaw SM, George C, Bellomo R. Early acute kidney injury and sepsis: a

multicentre evaluation. Crit Care 2008;12(2):R47.

  1. Kotecha A, Vallabhajosyula S, Coville HH, Kashani K. Cardiorenal syndrome in sepsis: a narrative review. J Crit Care 2017;43:122-7.
  2. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus def-

initions for sepsis and septic shock (sepsis-3). JAMA 2016;315(8):801-10.

  1. Rivers EP, Ahrens T. Improving outcomes for severe sepsis and septic shock: tools for early identification of at-risk patients and treatment protocol implementation. Crit Care Clin 2008;23:S1-S47.

Bias in the measurement of optic nerve sheath diameter

Raffiz et al. elegantly implemented a prospective observational study on the measurement of optic nerve sheath diameter in 2 patient groups: 21 traumatic and 20 non-traumatic patients with raised intracranial pressure confirmed by the placement of inva- sive intracranial pressure catheter – with a control group who were con- sidered to have clinically and radiologically normal ICP [1].

There is no doubt that ultrasonography is a valuable non-invasive tool to evaluate ONSD to determine intracranial pressure, considering the fact that the brain subarachnoid space is continuous with the optic nerve sheath and the pressure would be transmitted [2,3,4,5]. However, the way to measure the definite diameter is yet to be determined. Copetti et al. noted that the former measures were not compatible with the real anatomy of the optic nerve and proposed a new measure- ment that seems to be more reliable [2]. In a recent study of our group, there are two points to be considered:

  • According to the route of optic nerve approaching the globe, the oblique hypoechoic shadow running medially represents the exact measure of the optic nerve (Fig. 1).
  • Regarding Color Doppler ultrasonography of the central retinal artery, the new image compatible with the oblique hypoechoic shadow seems more characteristic of the optic nerve [6].

1. Pitfalls

Some reported measurements indicating an anechoic image behind retina was probably the artifact of lamina cribrosa, the mesh-like bony structure for optic nerve fibers’ passage through the sclera, mimicking optic nerve route [2].

Another pitfall is measuring the ill-defined non-clear shadow, prob- ably the previously discussed shadow superimposed on real ONSD. This

Fig. 1. ocular ultrasound with Linear probe 12 MHz in a normal subject shows the optic nerve diameter, identified with color Doppler that is 35 mm.

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