Critical Care Medicine

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ISSN / EISSN : 0090-3493 / 1530-0293
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, Antonio Pesenti, Mattia Busana, Stefano De Falco, Luca Di Girolamo, Eleonora Scotti, Ilaria Protti, Sebastiano Maria Colombo, Vittorio Scaravilli, Osvaldo Biancolilli, et al.
Abstract:
Objectives: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2 clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2 combined with continuous renal replacement therapy (CRRT). Design: Preclinical, proof-of-concept study. Setting: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase PCO2 and promote CO2 removal. Patients: Six, 38.7 ± 2.0-kg female pigs. Interventions: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial PCO2 at 50 mm Hg. Measurements and Main Results: Increasing acidification enhanced CO2 removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2 production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung PaO2 dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2 removal capability of the device, thus PaO2 decreased. Conclusions: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2 removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.
Hiroyuki Ohbe, Hiroki Matsui, Hideo Yasunaga
Abstract:
Objectives: To compare the outcomes of patients with acute myocardial infarction who were treated in ICUs versus high-dependency care units (HDUs). Design: A nationwide, propensity score-matched, retrospective cohort study of a national administrative inpatient database in Japan from July 2010 to March 2018. Setting: Six hundred sixty-six acute-care hospitals with ICU and/or HDU beds covering about 75% of all ICU beds and 70% of all HDU beds in Japan. Patients: Adult patients who were hospitalized for acute myocardial infarction and admitted to the ICU or HDU on the day of hospital admission. Propensity score-matching analysis was performed to compare the inhospital mortality between patients treated in the ICU and HDU on the day of hospital admission. Interventions: ICU or HDU admission on the day of hospital admission. Measurements and Main Results: Of 135,142 eligible patients, 89,382 (66%) were admitted to the ICU and 45,760 (34%) were admitted to the HDU on the day of admission. After propensity score matching, there was no statistically significant difference in inhospital mortality between the ICU and HDU groups (5.0% vs 5.5%; difference, –0.5%; 95% CI, –1.0% to 0.1%). In the subgroup analyses, inhospital mortality was significantly lower in the ICU group than that in the HDU group among patients with Killip class IV (25.6% vs 28.4%; difference, –2.9%; 95% CI, –5.4% to –0.3%), patients who underwent intubation (40.0% vs 46.6%; difference, –6.6%; 95% CI, –10.6% to –2.7%), and patients who received mechanical circulatory support (21.8% vs 24.7%; difference, –2.8%; 95% CI, –5.5% to –0.2%). Conclusions: Critical care in the ICU compared with that in the HDU was not associated with reduced inhospital mortality among the entire cohort of patients with acute myocardial infarction but was associated with reduced inhospital mortality among the subsets of patients with Killip class IV, intubation, or mechanical circulatory support.
Benjamin Seeliger, Michael Doebler, Daniel Andrea Hofmaenner, Pedro D. Wendel-Garcia, Reto A. Schuepbach, Julius J. Schmidt, Tobias Welte, Marius M. Hoeper, Hans-Jörg Gillmann, Christian Kuehn, et al.
Abstract:
Objectives: Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19–induced ARDS in comparison to viral non-COVID-19–induced ARDS intracerebral hemorrhage. Design: Multicenter, retrospective analysis between January 2010 and May 2021. Setting: Three tertiary care ECMO centers in Germany and Switzerland. Patients: Two-hundred ten ARDS patients on ECMO support (COVID-19, n = 142 vs viral non-COVID, n = 68). Interventions: None. Measurements and Main Results: Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9–17.8; p = 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%. Conclusions: This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.
Suelyn Van Den Helm, Hui Ping Yaw, Natasha Letunica, Rebecca Barton, Asami Weaver, Fiona Newall, Stephen B. Horton, Roberto Chiletti, Amy Johansen, Derek Best, et al.
Abstract:
Objectives: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO). Design: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019. Setting: The PICU in a large tertiary referral pediatric ECMO center. Patients: Eighty-seven neonates and children (< 18 yr) supported by ECMO. Interventions: None. Measurements and Main Results: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3–8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10–29 d) and 35 days (IQR, 19–75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020). Conclusions: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.
, Malory Favreau, Vincent Degos, Aymeric Amelot, Alexandre Le Joncour, Nicolas Weiss, Benjamin Rohaut, Loïc Le Guennec, Anne-Laure Boch, Alexandre Carpentier, et al.
Abstract:
Objectives: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context. Design: Monocenter, retrospective, observational cohort study. Setting: A French tertiary center. Patients: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients. Interventions: None. Measurements and Main Results: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4–3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01–2.6]; p = 0.04). Conclusions: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.
Matteo Di Nardo, Danilo Alunni Fegatelli, Marco Marano, Jacob Danoff,
Abstract:
Objectives: To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality. Design: Retrospective cohort study. Setting: Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019. Patients: Pediatric patients (0–18 yr) receiving ECMO for poisoning. Interventions: None. Measurements and Main Results: During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p< 0.01). A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13–17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated PaO2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0–58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0–60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively). Conclusions: ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated PaO2 after 24 hours of ECMO were associated with mortality.
Guosong Wu, Andrea Soo, Paul Ronksley, Jayna Holroyd-Leduc, Sean M. Bagshaw, Qunhong Wu, Hude Quan,
Abstract:
Objectives: To determine the incidence of falls, risk factors, and adverse outcomes, among patients admitted to the ICU. Design: Retrospective cohort study. Setting: Seventeen ICUs in Alberta, Canada. Patients: Seventy-three thousand four hundred ninety-five consecutive adult patient admissions between January 1, 2014, and December 31, 2019. Measurements and Main Results: A mixed-effects negative binomial regression model was used to examine risk factors associated with falls. Linear and logistic regression models were used to evaluate adverse outcomes. Six hundred forty patients experienced 710 falls over 398,223 patient days (incidence rate of 1.78 falls per 1,000 patient days [95% CI, 1.65–1.91]). The daily incidence of falls increased during the ICU stay (e.g., day 1 vs day 7; 0.51 vs 2.43 falls per 1,000 patient days) and varied significantly between ICUs (range, 0.37–4.64 falls per 1,000 patient days). Male sex (incidence rate ratio [IRR], 1.37; 95% CI, 1.15–1.63), previous invasive mechanical ventilation (IRR, 1.82; 95% CI, 1.40–2.38), previous sedative and analgesic medication infusions (IRR, 1.60; 95% CI, 1.15–2.24), delirium (IRR, 3.85; 95% CI, 3.23–4.58), and patient mobilization (IRR, 1.26; 95% CI, 1.21–1.30) were risk factors for falling. Falls were associated with longer ICU (ratio of means [RM], 3.10; 95% CI, 2.86–3.36) and hospital (RM, 2.21; 95% CI, 2.01–2.42) stays, but lower odds of death in the ICU (odds ratio [OR], 0.09; 95% CI, 0.05–0.17) and hospital (OR, 0.21; 95% CI, 0.14–0.30). Conclusions: We observed that among ICU patients, falls occur frequently, vary substantially between ICUs, and are associated with modifiable risk factors, longer ICU and hospital stays, and lower risk of death. Our study suggests that fall prevention strategies should be considered for critically ill patients admitted to ICU.
Ravindran Visagan, Florence R. A. Hogg, Mathew J. Gallagher, Siobhan Kearney, Argyro Zoumprouli, Marios C. Papadopoulos,
Abstract:
Objectives: To determine the feasibility of monitoring tissue oxygen tension from the injury site (psctO2) in patients with acute, severe traumatic spinal cord injuries. Design: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and psctO2. We analyzed 2,213 hours of such data. Follow-up was 6–28 months postinjury. Setting: Single-center neurosurgical and neurocritical care units. Subjects: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A–C. Probes were inserted within 72 hours of injury. Interventions: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter. Measurements and Main Results: psctO2 was significantly influenced by ISP (psctO2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs psctO2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (psctO2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs psctO2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (psctO2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (psctO2 25.3 ± 0.4 mm Hg at LPR > 30 vs psctO2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (psctO2 28.8 ± 0.5 mm Hg at cord temperature 37–38°C vs psctO2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the FIO2 by 0.48 increases psctO2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in psctO2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at psctO2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at psctO2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26). Conclusions: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.
Michelle W. Rudolph, , Lisa A. Asaro, Ira M. Cheifetz, David Wypij, Martha A. Q. Curley
Abstract:
Objectives: The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without. Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation. Setting: Thirty-one PICUs in the United States. Patients: Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index ≥ 8 and bilateral infiltrates on chest radiograph on days 0–1 of endotracheal intubation). Interventions: NMBA for the entire duration of days 1 and 2 after intubation. Measurements and Main Results: Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3–60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0–2 (odds ratio [OR], 7.61; 95% CI, 4.75–12.21) and severe PARDS on days 0–1 (OR, 2.16; 95% CI, 1.50–3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48–0.68; p< 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92–2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline PaO2/FIO2 less than 150. Conclusions: Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics.
Michaelia D. Cucci, Katleen W. Chester, Leslie A. Hamilton
Abstract:
Objective: Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients. Data Sources: Available literature on PubMed and MEDLINE databases. Study Selection: Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included. Data Extraction: Eligible studies were identified by authors, and recommendations were summarized. Data Synthesis: Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay. Conclusions: Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.
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