The sicker the patient, the higher the mortality

Abstract

To the editor,

We read with interest the recent published article by Gajardo et al. titled “Early high-sensitivity troponin elevation and short-term mortality in sepsis: a systematic review with meta-analysis” [1]. The authors provide us with an interesting and well written review of the literature regarding the prognostic value of elevated serum high-sensitivity cardiac troponin (hs-cTn). The authors conclude that even though hs-cTn is overall associated with increased mortality, this association is attenuated when corrected for potential confounders.

The availability of articles that try to establish the prognostic value of an essay known to represent cardiac damage is surprising. In our opinion, the articles used for this review demonstrate a simple principle like most other prognostication articles: ‘the sicker patient, the higher the mortality’. Numerous articles have found associations between deviation from normal physiology in ICU patients (or in specific patient groups like septic patients) and mortality. It is not surprising that elevation of a marker indicating myocardial damage is associated with poorer outcome.

There have been countless articles published with this principle. Our most extensively used prognostic model, the SOFA score [2], is the prime example. The more extensive the organ failure, the higher mortality. Separating the organ systems used in the SOFA score results in more studies with associations between deranged physiology and mortality. For example in patients with acute respiratory distress syndrome (ARDS) higher oxygen demand to maintain acceptable paO₂ is associated with higher mortality [3]. And patients with acute renal failure are known to have poorer prognoses than patients with normal renal function [4]. Again, perfect examples of “the sicker the patient, the higher the mortality” where the presence and severity of organ failure predict mortality.

Virtually all biochemical parameters have been studied to find associations between deviations from normal and mortality. Along with hypernatremia [5], associations with mortality were found with low albumin levels [6], elevated phosphate [7], elevated triglyceride levels [8] and elevated amylase [9]. These are only a few examples of laboratory results that have been investigated and they all come down to the same old song: ‘the sicker the patient, the higher mortality’.

From a research point of view the stratification of patients in prognostic different classes (i.e. severities of illness) is understandable. In for example ARDS patients it could be useful to stratify for severity of illness when studying ventilation strategies, because the greatest treatment effects are expected in the sickest patients. But one has to keep in mind that the cut off values created in studies are just that, created. A result of creating these cut-off points is that guidelines base their recommendations on study stratifications. But does it really matter if a patient has a P/F ratio of 151 mmHg or 149 mmHg, even though prognostication studies suggest that with a P/F ratio of 149 mmHg the mortality will be higher, merely due to stratification in the study design?

Furthermore, finding an association between a deviation from normal physiology and mortality does not mean treating these abnormalities lead to improved outcome. The abnormalities are typically epiphenomena of the underlying illness and, in themselves, are not the direct cause of increased mortality. For example, routinely supplementing albumin in hypoalbuminemia in sepsis has not shown to improve mortality outcomes [10] and various studies have shown that higher targets in anemia lead to increased mortality [11].

This study of Gajardo et al. demonstrates this as well. Elevation of hs-cTn is a sign of cardiac damage, harm that is already done. We have to acknowledge myocardial infarction early in the disease, but in sepsis, like the authors wrote, cardiac damage is often multifactorial, without specific treatment options, besides treating the underlying disease. Treating myocardial infarction helps the patient, but prognostication based on a cardiac marker does not.

The physiology of the ill is different than the physiology of the healthy. The sicker the patient is, the more the physiology deviates from the healthy, leading to more pronounced biochemical abnormalities. And the sicker the patient, the higher the mortality. While these principles are straightforward and valuable for stratification purposes, they provide limited guidance when it comes to treating individual patients.

Observational studies trying to find associations between readily available blood tests and mortality may be the low-hanging fruit of literature, but maybe, just maybe, we should try to accept that prognostication studies usually demonstrate that if a patient is sicker, the chances of dying are higher.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

1. Department of Critical Care, Martini Hospital, Van Swietenplein 1, 9728 NT, Groningen, The Netherlands

   Hendrik Wietse Zijlstra, Wilhelmina Aria Christina Koekkoek & Esther Karlijn Haspels

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All authors have made substantial contribution to writing process. HWZ wrote the draft. All authors provided critical feedback, contributed substantially to the final version and take full responsibility for the content of the paper.

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Correspondence to Hendrik Wietse Zijlstra.

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Zijlstra, H.W., Koekkoek, W.A.C. & Haspels, E.K. The sicker the patient, the higher the mortality. Crit Care 29, 118 (2025). https://doi.org/10.1186/s13054-025-05355-1

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• Received: 28 February 2025

• Accepted: 04 March 2025

• Published: 18 March 2025

• DOI: https://doi.org/10.1186/s13054-025-05355-1

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