Early exercise therapy in patients with severe traumatic spinal cord injury: is it feasible in the ICU?

IF 8.8 1区 医学 Q1 CRITICAL CARE MEDICINE
Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong
{"title":"Early exercise therapy in patients with severe traumatic spinal cord injury: is it feasible in the ICU?","authors":"Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong","doi":"10.1186/s13054-025-05297-8","DOIUrl":null,"url":null,"abstract":"<p>Following traumatic spinal cord injury (SCI), patients remain immobilized in the intensive care unit (ICU) and the wards for several weeks before they are transferred to rehabilitation [1]. Unfortunately, this places them at high risk for deconditioning and developing immobility-associated complications [2]. In addition, immobility during the acute stages after TSCI could potentially hinder adaptive neuroplasticity and limit long-term neurological recovery, while early mobilization/exercise could improve outcomes [3]. Until now, early exercise therapy (EET) had never been attempted in humans due to practical obstacles for bedridden patients and potential concerns for safety, especially for patients in the ICU. In this context, the PROMPT-SCI trial is the first trial designed to evaluate the safety and feasibility of EET in patients with acute severe TSCI (ClinicalTrials.gov: NCT04699474) [4]. In this Correspondence, we aim to report specifically on our patients who were hospitalized in the ICU.</p><p>As part of the PROMPT-SCI trial, 45 adult patients were recruited from a single Level-1 trauma center in Montreal, Canada, between April 2021 and August 2023. All had sustained a severe TSCI leading to an American Spinal Injury Association Impairment Scale (AIS) grade A, B or C injury. After immediate medical stabilization and resuscitation, MAP therapy was instituted (target MAP≈ 85 mmHg) and surgery was performed within 48 h to decompress the spinal cord and stabilize the spine. The intervention consisted of daily 30-min sessions of continuous passive in-bed leg cycling for 14 consecutive days, starting within 48 h of surgery based on the initiation criteria described in Table 1. During cycling, MAP, heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO2) were monitored, and adverse events were noted. Sessions were stopped if patients requested termination, if vital signs fluctuated outside of the following ranges in a sustained fashion: MAP: 60–110 mmHg; HR: 40–140 bpm; SpO2: ≥ 90%, or if there were other signs of medical instability (e.g.hypo/hypertension, cardiac anomaly, etc.). Vasopressors were titrated to achieve a MAP≈ 85 mmHg and maintained at stable levels during sessions. After each session, complete neurological exams were performed to ensure safety.</p><figure><figcaption><b data-test=\"table-caption\">Table 1 Baseline characteristics of the 40 ICU patients who participated in the PROMPT-SCI trial</b></figcaption><span>Full size table</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Forty participants initiated the 14-day protocol in the ICU within 3 days of the SCI. Of these 40 participants, 33 (82.5%) managed to complete their first full session of cycling &lt; 48 h after spine surgery, while the 7 remaining patients managed to do so the next day (&lt; 72 h of surgery). Of these 7, 5 did not initiate cycling &lt; 48 h post-op (2 were intubated and required a high degree of medical attention, 2 had scheduling conflicts due to investigations or therapeutic activities related to care and 1 refused due to fatigue/pain) and the other 2 initiated a session but it was interrupted prematurely (1 due to pre-existing abdominal pain that persisted with cycling and 1 due to prolonged SpO2 &lt; 89% that resolved spontaneously after termination).</p><p>Over the remainder of the protocol, there were 366 potential sessions for our 40 ICU patients. Of these 366 sessions, 55 were not attempted (15.0%) and 5 (1.4%) were initiated but terminated prematurely (overall completion rate = 83.6%). Most frequent reasons for unattempted sessions were: medical instability as per caring team (n = 11), pressure injury (n = 8) and patient refusal due to pain/fatigue (n = 11). Reasons for stopping sessions were: persistent pre-existing abdominal pain or pain at surgical site (n = 3), prolonged SpO2 &lt; 89% (n = 1) and conflicting schedule (n = 1; planned bronchoscopy). In addition, we report no major adverse event related to cycling.</p><p>Also, of our 40 ICU participants, 3 were mechanically ventilated during the protocol. While 2 initiated cycling only 72 h post-op, these 3 patients had a 100% completion rate with no deviation to the protocol thereafter.</p><p>In terms of average cardiorespiratory response to cycling, we observed no increase in HR (69.6 ± 14.5 rest vs. 69.9 ± 14.6 cycling; p = 0.351), a small increase in MAP (88.7 ± 11.4 rest vs. 89.6 ± 11.1 cycling; p = 0.037), a small increase in RR (20.3 ± 5.8 rest vs. 21.6 ± 5.1 cycling; p &lt; 0.001) and a small decrease in SpO2 (97.0 ± 2.1 rest vs. 95.9 ± 2.9 cycling; p &lt; 0.001), confirming that passive in-bed leg cycling is a form of low-intensity exercise, which possibly helps limit the neurological risk [5]. However, at the individual level, we do report significant increases in MAP &gt; 10 mmHg (and up to 30 mmHg) with the initiation of cycling in the majority of our patients (n = 35), but these were never significant enough to warrant premature termination of cycling based on the stopping criteria described above. In addition, post-hoc analyses did not show any relation between these MAP increases and timing of sessions (first sessions vs later sessions). We also observed that 70% of MAP increases &gt; 10 mmHg occurred in patients with neurological lesions above T7, which predispose to autonomic dyssynergia and dysreflexia.</p><p>In conclusion, this study supports the safety and feasibility of passive in-bed leg cycling in ICU patients with severe TSCI. We recommend close monitoring of MAP during sessions, especially for patients with lesions above T7.</p><p>The datasets that were generated during the course of this research are available from the corresponding author upon reasonable request.</p><dl><dt style=\"min-width:50px;\"><dfn>AIS:</dfn></dt><dd>\n<p>American spinal injury association impairment scale</p>\n</dd><dt style=\"min-width:50px;\"><dfn>EET:</dfn></dt><dd>\n<p>Early exercise therapy</p>\n</dd><dt style=\"min-width:50px;\"><dfn>HR:</dfn></dt><dd>\n<p>Heart rate</p>\n</dd><dt style=\"min-width:50px;\"><dfn>ICU:</dfn></dt><dd>\n<p>Intensive care unit</p>\n</dd><dt style=\"min-width:50px;\"><dfn>MAP:</dfn></dt><dd>\n<p>Mean arterial pressure</p>\n</dd><dt style=\"min-width:50px;\"><dfn>PROMPT-SCI:</dfn></dt><dd>\n<p>Protocol for rapid onset of mobilization in patients with traumatic spinal cord injury</p>\n</dd><dt style=\"min-width:50px;\"><dfn>RR:</dfn></dt><dd>\n<p>Respiratory rate</p>\n</dd><dt style=\"min-width:50px;\"><dfn>SCI:</dfn></dt><dd>\n<p>Spinal cord injury</p>\n</dd><dt style=\"min-width:50px;\"><dfn>SpO2:</dfn></dt><dd>\n<p>Blood oxygen saturation</p>\n</dd><dt style=\"min-width:50px;\"><dfn>TSCI:</dfn></dt><dd>\n<p>Traumatic spinal cord injury</p>\n</dd></dl><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Cheng CL, Plashkes T, Shen T, Fallah N, Humphreys S, O’Connell C, et al. Does specialized inpatient rehabilitation affect whether or not people with traumatic spinal cord injury return home? J Neurotrauma. 2017;34(20):2867–76.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"2.\"><p>Ahuja CS, Wilson JR, Nori S, Kotter MRN, Druschel C, Curt A, et al. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017;3:17018.</p><p>Article PubMed Google Scholar </p></li><li data-counter=\"3.\"><p>Brown AK, Woller SA, Moreno G, Grau JW, Hook MA. Exercise therapy and recovery after SCI: evidence that shows early intervention improves recovery of function. Spinal Cord. 2011;49(5):623–8.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li><li data-counter=\"4.\"><p>Mac-Thiong JM, Richard-Denis A, Petit Y, Bernard F, Barthélémy D, Dionne A, Magnuson D. Protocol for rapid onset of mobilization in patients with traumatic spinal cord injury (PROMPT-SCI) study: a single-arm proof-of-concept trial of early in-bed leg cycling following acute traumatic spinal cord injury. British Medical Journal Open. 2021; Accepted.</p></li><li data-counter=\"5.\"><p>Medrinal C, Combret Y, Prieur G, Robledo Quesada A, Bonnevie T, Gravier FE, et al. Comparison of exercise intensity during four early rehabilitation techniques in sedated and ventilated patients in ICU: a randomised cross-over trial. Crit Care. 2018;22(1):110.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><p>We thank the research personnel at the Laboratoire d’Orthopédie-Colonne de l’Hôpital du Sacré-Coeur de Montréal for their contribution to this project. We also thank the study participants, without whom this research would not have been possible.</p><p>This research was funded by the Craig H. Neilsen foundation.</p><h3>Authors and Affiliations</h3><ol><li><p>Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, QC, Canada</p><p>Antoine Dionne, Andréane Richard-Denis, Francis Bernard &amp; Jean-Marc Mac-Thiong</p></li><li><p>Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin Boul. Ouest, Montreal, QC, H4J 1C5, Canada</p><p>Antoine Dionne, Andréane Richard-Denis, Yvan Petit, Francis Bernard &amp; Jean-Marc Mac-Thiong</p></li><li><p>Sainte-Justine University Hospital Research Center, Montreal, QC, Canada</p><p>Jean-Marc Mac-Thiong</p></li><li><p>Department of Neurological Surgery, University of Louisville, Louisville, KY, USA</p><p>David Magnuson</p></li><li><p>Department of Mechanical Engineering, École de Technologie Supérieure, Montreal, QC, Canada</p><p>Yvan Petit</p></li><li><p>Center for Interdisciplinary Research in Rehabilitation of Greater Montreal, CRIR, Montreal, QC, Canada</p><p>Dorothy Barthélémy</p></li><li><p>Faculty of Medicine, School of Rehabilitation, University of Montreal, Montreal, QC, Canada</p><p>Dorothy Barthélémy</p></li></ol><span>Authors</span><ol><li><span>Antoine Dionne</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>David Magnuson</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Andréane Richard-Denis</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Yvan Petit</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Dorothy Barthélémy</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Francis Bernard</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Jean-Marc Mac-Thiong</span>View author publications<p><span>You can also search for this author in</span><span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Contributions</h3><p>AD was responsible for designing the study, collecting the data, performing the statistical analyses, interpreting the results and drafting the manuscript. DSK, ARD, DB, FB and YP were responsible for designing the study, interpreting the results and reviewing the manuscript.\nJMMT was responsible for designing the study, interpreting the results, reviewing the final manuscript and securing funding.</p><h3>Corresponding author</h3><p>Correspondence to Jean-Marc Mac-Thiong.</p><h3>Ethical approval and informed consent</h3>\n<p>All patients provided informed written consent before enrollment. This study was approved by the <i>Comité d’Éthique de la recherche du CIUSSS du Nord-de-L’Île de Montréal</i> (“Mobilisation précoce suite à une lésion médullaire”, study #2020–1901, approved on March 12th, 2020) and was conducted in accordance with the principles of the Declaration of Helsinki.</p><h3>Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.</p>\n<p>Reprints and permissions</p><img alt=\"Check for updates. 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Early exercise therapy in patients with severe traumatic spinal cord injury: is it feasible in the ICU?. <i>Crit Care</i> <b>29</b>, 120 (2025). https://doi.org/10.1186/s13054-025-05297-8</p><p>Download citation<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><ul data-test=\"publication-history\"><li><p>Received<span>: </span><span><time datetime=\"2025-01-18\">18 January 2025</time></span></p></li><li><p>Accepted<span>: </span><span><time datetime=\"2025-01-22\">22 January 2025</time></span></p></li><li><p>Published<span>: </span><span><time datetime=\"2025-03-18\">18 March 2025</time></span></p></li><li><p>DOI</abbr><span>: </span><span>https://doi.org/10.1186/s13054-025-05297-8</span></p></li></ul><h3>Share this article</h3><p>Anyone you share the following link with will be able to read this content:</p><button data-track=\"click\" 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Abstract

Following traumatic spinal cord injury (SCI), patients remain immobilized in the intensive care unit (ICU) and the wards for several weeks before they are transferred to rehabilitation [1]. Unfortunately, this places them at high risk for deconditioning and developing immobility-associated complications [2]. In addition, immobility during the acute stages after TSCI could potentially hinder adaptive neuroplasticity and limit long-term neurological recovery, while early mobilization/exercise could improve outcomes [3]. Until now, early exercise therapy (EET) had never been attempted in humans due to practical obstacles for bedridden patients and potential concerns for safety, especially for patients in the ICU. In this context, the PROMPT-SCI trial is the first trial designed to evaluate the safety and feasibility of EET in patients with acute severe TSCI (ClinicalTrials.gov: NCT04699474) [4]. In this Correspondence, we aim to report specifically on our patients who were hospitalized in the ICU.

As part of the PROMPT-SCI trial, 45 adult patients were recruited from a single Level-1 trauma center in Montreal, Canada, between April 2021 and August 2023. All had sustained a severe TSCI leading to an American Spinal Injury Association Impairment Scale (AIS) grade A, B or C injury. After immediate medical stabilization and resuscitation, MAP therapy was instituted (target MAP≈ 85 mmHg) and surgery was performed within 48 h to decompress the spinal cord and stabilize the spine. The intervention consisted of daily 30-min sessions of continuous passive in-bed leg cycling for 14 consecutive days, starting within 48 h of surgery based on the initiation criteria described in Table 1. During cycling, MAP, heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO2) were monitored, and adverse events were noted. Sessions were stopped if patients requested termination, if vital signs fluctuated outside of the following ranges in a sustained fashion: MAP: 60–110 mmHg; HR: 40–140 bpm; SpO2: ≥ 90%, or if there were other signs of medical instability (e.g.hypo/hypertension, cardiac anomaly, etc.). Vasopressors were titrated to achieve a MAP≈ 85 mmHg and maintained at stable levels during sessions. After each session, complete neurological exams were performed to ensure safety.

Table 1 Baseline characteristics of the 40 ICU patients who participated in the PROMPT-SCI trial
Full size table

Forty participants initiated the 14-day protocol in the ICU within 3 days of the SCI. Of these 40 participants, 33 (82.5%) managed to complete their first full session of cycling < 48 h after spine surgery, while the 7 remaining patients managed to do so the next day (< 72 h of surgery). Of these 7, 5 did not initiate cycling < 48 h post-op (2 were intubated and required a high degree of medical attention, 2 had scheduling conflicts due to investigations or therapeutic activities related to care and 1 refused due to fatigue/pain) and the other 2 initiated a session but it was interrupted prematurely (1 due to pre-existing abdominal pain that persisted with cycling and 1 due to prolonged SpO2 < 89% that resolved spontaneously after termination).

Over the remainder of the protocol, there were 366 potential sessions for our 40 ICU patients. Of these 366 sessions, 55 were not attempted (15.0%) and 5 (1.4%) were initiated but terminated prematurely (overall completion rate = 83.6%). Most frequent reasons for unattempted sessions were: medical instability as per caring team (n = 11), pressure injury (n = 8) and patient refusal due to pain/fatigue (n = 11). Reasons for stopping sessions were: persistent pre-existing abdominal pain or pain at surgical site (n = 3), prolonged SpO2 < 89% (n = 1) and conflicting schedule (n = 1; planned bronchoscopy). In addition, we report no major adverse event related to cycling.

Also, of our 40 ICU participants, 3 were mechanically ventilated during the protocol. While 2 initiated cycling only 72 h post-op, these 3 patients had a 100% completion rate with no deviation to the protocol thereafter.

In terms of average cardiorespiratory response to cycling, we observed no increase in HR (69.6 ± 14.5 rest vs. 69.9 ± 14.6 cycling; p = 0.351), a small increase in MAP (88.7 ± 11.4 rest vs. 89.6 ± 11.1 cycling; p = 0.037), a small increase in RR (20.3 ± 5.8 rest vs. 21.6 ± 5.1 cycling; p < 0.001) and a small decrease in SpO2 (97.0 ± 2.1 rest vs. 95.9 ± 2.9 cycling; p < 0.001), confirming that passive in-bed leg cycling is a form of low-intensity exercise, which possibly helps limit the neurological risk [5]. However, at the individual level, we do report significant increases in MAP > 10 mmHg (and up to 30 mmHg) with the initiation of cycling in the majority of our patients (n = 35), but these were never significant enough to warrant premature termination of cycling based on the stopping criteria described above. In addition, post-hoc analyses did not show any relation between these MAP increases and timing of sessions (first sessions vs later sessions). We also observed that 70% of MAP increases > 10 mmHg occurred in patients with neurological lesions above T7, which predispose to autonomic dyssynergia and dysreflexia.

In conclusion, this study supports the safety and feasibility of passive in-bed leg cycling in ICU patients with severe TSCI. We recommend close monitoring of MAP during sessions, especially for patients with lesions above T7.

The datasets that were generated during the course of this research are available from the corresponding author upon reasonable request.

AIS:

American spinal injury association impairment scale

EET:

Early exercise therapy

HR:

Heart rate

ICU:

Intensive care unit

MAP:

Mean arterial pressure

PROMPT-SCI:

Protocol for rapid onset of mobilization in patients with traumatic spinal cord injury

RR:

Respiratory rate

SCI:

Spinal cord injury

SpO2:

Blood oxygen saturation

TSCI:

Traumatic spinal cord injury

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  4. Mac-Thiong JM, Richard-Denis A, Petit Y, Bernard F, Barthélémy D, Dionne A, Magnuson D. Protocol for rapid onset of mobilization in patients with traumatic spinal cord injury (PROMPT-SCI) study: a single-arm proof-of-concept trial of early in-bed leg cycling following acute traumatic spinal cord injury. British Medical Journal Open. 2021; Accepted.

  5. Medrinal C, Combret Y, Prieur G, Robledo Quesada A, Bonnevie T, Gravier FE, et al. Comparison of exercise intensity during four early rehabilitation techniques in sedated and ventilated patients in ICU: a randomised cross-over trial. Crit Care. 2018;22(1):110.

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We thank the research personnel at the Laboratoire d’Orthopédie-Colonne de l’Hôpital du Sacré-Coeur de Montréal for their contribution to this project. We also thank the study participants, without whom this research would not have been possible.

This research was funded by the Craig H. Neilsen foundation.

Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, QC, Canada

    Antoine Dionne, Andréane Richard-Denis, Francis Bernard & Jean-Marc Mac-Thiong

  2. Research Center, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin Boul. Ouest, Montreal, QC, H4J 1C5, Canada

    Antoine Dionne, Andréane Richard-Denis, Yvan Petit, Francis Bernard & Jean-Marc Mac-Thiong

  3. Sainte-Justine University Hospital Research Center, Montreal, QC, Canada

    Jean-Marc Mac-Thiong

  4. Department of Neurological Surgery, University of Louisville, Louisville, KY, USA

    David Magnuson

  5. Department of Mechanical Engineering, École de Technologie Supérieure, Montreal, QC, Canada

    Yvan Petit

  6. Center for Interdisciplinary Research in Rehabilitation of Greater Montreal, CRIR, Montreal, QC, Canada

    Dorothy Barthélémy

  7. Faculty of Medicine, School of Rehabilitation, University of Montreal, Montreal, QC, Canada

    Dorothy Barthélémy

Authors
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  4. Yvan PetitView author publications

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Contributions

AD was responsible for designing the study, collecting the data, performing the statistical analyses, interpreting the results and drafting the manuscript. DSK, ARD, DB, FB and YP were responsible for designing the study, interpreting the results and reviewing the manuscript. JMMT was responsible for designing the study, interpreting the results, reviewing the final manuscript and securing funding.

Corresponding author

Correspondence to Jean-Marc Mac-Thiong.

Ethical approval and informed consent

All patients provided informed written consent before enrollment. This study was approved by the Comité d’Éthique de la recherche du CIUSSS du Nord-de-L’Île de Montréal (“Mobilisation précoce suite à une lésion médullaire”, study #2020–1901, approved on March 12th, 2020) and was conducted in accordance with the principles of the Declaration of Helsinki.

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Dionne, A., Magnuson, D., Richard-Denis, A. et al. Early exercise therapy in patients with severe traumatic spinal cord injury: is it feasible in the ICU?. Crit Care 29, 120 (2025). https://doi.org/10.1186/s13054-025-05297-8

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来源期刊
Critical Care
Critical Care 医学-危重病医学
CiteScore
20.60
自引率
3.30%
发文量
348
审稿时长
1.5 months
期刊介绍: Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.
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