Association of early dexmedetomidine exposure with brain injury biomarker levels following moderate - Severe traumatic brain injury: A TRACK-TBI study.

BACKGROUND: Traumatic brain injury (TBI) triggers autonomic dysfunction and inflammatory response that can result in secondary brain injuries. Dexmedetomidine is an alpha-2 agonist that may modulate autonomic function and inflammation and has been increasingly used as a sedative agent for critically ill TBI patients. We aimed to investigate the association between early dexmedetomidine exposure and blood-based biomarker levels in moderate-to-severe TBI (msTBI). METHODS: We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study (TRACK-TBI), which enrolled acute TBI patients prospectively across 18 United States Level 1 trauma centers between 2014-2018. Our study population focused on adults with msTBI defined by Glasgow Coma Scale score 3-12 after resuscitation, who required mechanical ventilation and sedation within the first 48 h of ICU admission. The study's exposure was early dexmedetomidine utilization (within the first 48 h of admission). Primary outcome included brain injury biomarker levels measured from circulating blood on day 3 following injury, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and the inflammatory biomarker C-reactive protein (CRP). Secondary outcomes assessed biomarker levels on days 5 and 14. Linear mixed-effects regression modelling of the log-transformed response variable was used to analyze the association of early dexmedetomidine exposure with brain injury biomarker levels. RESULTS: Among the 352 TRACK-TBI subjects that met inclusion criteria, 50 (14.2 %) were exposed to early dexmedetomidine, predominantly male (78 %), white (81 %), and non-Hispanic (81 %), with mean age of 39.8 years. Motor vehicle collisions (27 %) and falls (22 %) were common causes of injury. No significant associations were found between early dexmedetomidine exposure with day 3 brain injury biomarker levels (GFAP, ratio = 1.46, 95 % confidence interval [0.90, 2.34], P = 0.12; UCH-L1; ratio = 1.17 [0.89, 1.53], P = 0.26; NSE, ratio = 1.19 [0.92, 1.53], P = 0.19; S100B, ratio = 1.01 [0.95, 1.06], P = 0.82; hs-CRP, ratio = 1.29 [0.91, 1.83], P = 0.15). The hs-CRP level at day 14 in the dexmedetomidine group was higher than that of the non-exposure group (ratio = 1.62 [1.12, 2.35], P = 0.012). CONCLUSIONS: There were no significant associations between early dexmedetomidine exposure and day 3 brain injury biomarkers in msTBI. Our findings suggest that early dexmedetomidine use is not correlated with either decrease or increase in brain injury biomarkers following msTBI. Further research is necessary to confirm these findings.

Perioperative Albumin Among Adults Undergoing Thoracic Surgery in the United States: Utilization, Associations With Clinical Outcomes, and Contribution to Hospital Costs.

OBJECTIVES: To estimate the use of albumin among adults undergoing thoracic surgery in the United States, compare baseline characteristics, clinical and cost outcomes of recipients versus nonrecipients, and determine albumin's contribution to total hospital costs. DESIGN: Retrospective cohort study. SETTING: Nationwide sample of US hospitals. PARTICIPANTS: Adults undergoing open and minimally invasive thoracic surgery between 2011 and 2017. INTERVENTIONS: Albumin on the day of surgery (identified using itemized hospital billing logs). MEASUREMENTS AND MAIN RESULTS: Albumin was used in 170 of 342 US hospitals, among 13% and 7% of 14,672 and 22,532 patients who, respectively, underwent open and minimally invasive thoracic surgery (median volume 500 mL). Baseline comorbidities and organ-supportive treatments were several-fold more prevalent among recipients (particularly vasopressors, mechanical ventilation, and red cell transfusions). In standardized mortality ratio propensity score weighted analysis, albumin use was not associated with in-hospital mortality (adjusted relative risk 1.17 [0.72, 1.92] and 1.51 [0.97, 2.34], with open and minimally invasive procedures), but was associated with morbidity and higher costs, more so with minimally invasive procedures than with open surgery. Total costs among recipients were higher by $4,744 ($3,591, $5,897) and $5,088 ($4,075, $6,100) for open and minimally invasive procedures, respectively. Albumin accounted for 2.6% of this difference (median $124 [$83-$189] per patient). CONCLUSIONS: Albumin use varies widely across hospitals, and 9% of patients receive it (median 500 mL). Use was not associated with in-hospital mortality and was associated with more morbidity and cost. The cost of albumin accounted for a trivial portion of hospital costs. Clinical trials must examine the effects of albumin on complications and costs after thoracic surgery.

Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Trends in the Utilization of Multiorgan Support Among Adults Undergoing High-risk Cardiac Surgery in the United States.

OBJECTIVES: To examine trends in the prevalence of multiorgan dysfunction (MODS), utilization of multi-organ support (MOS), and mortality among patients undergoing cardiac surgery with MODS who received MOS in the United States. DESIGN: Retrospective cohort study. SETTING: 183 hospitals in the Premier Healthcare Database. PARTICIPANTS: Adults ≥18 years old undergoing high-risk elective or non-elective cardiac surgery. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: The exposure was time (consecutive calendar quarters) January 2008 and June 2018. We analyzed hospital data using day-stamped hospital billing codes and diagnosis and procedure codes to assess MODS prevalence, MOS utilization, and mortality. Among 129,102 elective and 136,190 non-elective high-risk cardiac surgical cases across 183 hospitals, 10,001 (7.7%) and 21,556 (15.8%) of patients developed MODS, respectively. Among patients who experienced MODS, 2,181 (22%) of elective and 5,425 (25%) of non-elective cardiac surgical cases utilized MOS. From 2008-2018, MODS increased in both high-risk elective and non-elective cardiac surgical cases. Similarly, MOS increased in both high-risk elective and non-elective cardiac surgical cases. As a component of MOS, mechanical circulatory support (MCS) increased over time. Over the study period, risk-adjusted mortality, in patients who developed MODS receiving MOS, increased in high-risk non-elective cardiac surgery and decreased in high-risk elective cardiac surgery, despite increasing MODS prevalence and MOS utilization (p<0.001). CONCLUSIONS: Among patients undergoing high-risk cardiac surgery in the United States, MODS prevalence and MOS utilization (including MCS) increased over time. Risk-adjusted mortality trends differed in elective and non-elective cardiac surgery. Further research is necessary to optimize outcomes among patients undergoing high-risk cardiac surgery.

Factors associated with 30-day mortality after perioperative cardiac arrest in adults undergoing non-cardiac surgery: a seven-year observational study from Siriraj Hospital.

Background: Perioperative cardiac arrest (PCA) in non-cardiac surgery patients is a rare but potentially catastrophic event with high mortality. Several studies highlighted factors contributing to PCA within the surgical population, but information on its outcomes remains limited. This study sought to identify independent factors associated with 30-day mortality after PCA in adults undergoing non-cardiac surgery. Methods: A retrospective cohort study was performed to identify these factors, PCA incidence, and incidence of 30-day mortality in non-cardiac surgery patients between 2015 to 2021 at Siriraj Hospital. Data collection entailed patient characteristics, surgical and anesthetic procedures, cardiac arrest details, and outcomes. Univariable and multivariable logistic regression analyses were performed to identify risk factors. Results: One hundred and five PCA cases from the Siriraj Hospital database were assessed from 259,372 anesthesia cases. Independent risk factors significantly associated with 30-day mortality included: preoperative vasopressor use [adjusted relative risk (aRR) 1.90, 95% CI: 1.08-3.32, P=0.025], cardiopulmonary resuscitation (CPR) outside a monitored setting (aRR 1.85, 95% CI: 1.08-3.17, P=0.025), and administering CPR for >15 minutes (aRR 1.97, 95% CI: 1.08-3.57, P=0.027). Univariable analysis found that a physical status classification of four to five by the American Society of Anesthesiologists and use of emergency procedures were also associated with 30-day mortality after PCA. Subgroup analysis revealed that in the emergency group, CPR durations >15 minutes were significantly associated with increased 30-day mortality (aRR 2.05, 95% CI: 1.29-3.28, P=0.003). Overall incidences of PCA and 30-day mortality after PCA were 4.31 per 10,000 and 2.00 per 10,000 cases, respectively. The one-year mortality rate for patients who experienced PCA was 67.6%. The most common cause was hypovolemia (18.1%), followed by acute coronary syndrome (13.3%). Conclusions: Preoperative vasopressor use was a pre-arrest contributing factor to 30-day mortality after PCA. Performing CPR outside a monitored setting and administering CPR for >15 minutes were two intra-arrest factors strongly linked to decreased survivability. While these factors are difficult to modify, vigilant monitoring of high-risk patients before PCA occurs and early detection of PCA, along with prompt and aggressive intervention, may improve patient outcomes.

Perioperative immediate hypersensitivity incidence, clinical characteristics, and outcomes after allergological evaluation: A multi-disciplinary protocol from tertiary hospital, Thailand.

BACKGROUND: Perioperative immediate hypersensitivity reaction (POH) is an immediate hypersensitivity reaction during an anesthesiologist monitored procedure. We report data of clinically-suspected POH (csPOH) patients undergoing an allergist-performed unified diagnostic workup algorithm for POH. OBJECTIVE: To describe the characteristics of patients with csPOH, POH events, and the POH outcomes of procedures after the unified diagnostic workup algorithm for POH. METHODS: A prospective cohort was conducted in adult patients with csPOH at Siriraj Hospital, a tertiary hospital, in Thailand from January 2018 to August 2022. Diagnostic workup for POH by the allergist included an initial assessment, followed by comprehensive allergological evaluation. Patients were then follow-up for POH outcomes during subsequent anesthesia procedures. RESULTS: Of 68 patients were csPOH, only 52 patients were diagnosed with POH by allergists. The incidence was 1:4,304 anesthetic procedures for POH, and 1:11,900 anesthetic procedures for at least grade III POH. Most patients had a grade III (51.2%) or II (46.4%) reaction. The leading identified causative agents were antibiotics (36.8%), antiseptics (21%), latex (13.1%), and morphine (13.1%). Cefazolin and chlorhexidine were the most common antibiotic and antiseptic, respectively. During a median follow-up time of 2.1 years, all 14 patients completing comprehensive allergological evaluation underwent subsequent anesthesia without recurrence of POH. CONCLUSIONS: The incidence of POH at our hospital was comparable to the global incidence. Antibiotics were the most common causative agent. Complete records, collaboration among the multidisciplinary team, and comprehensive evaluation of POH allow for safe subsequent procedures.

H1 and H2 antihistamines pretreatment for attenuation of protamine reactions after cardiopulmonary bypass: a randomized-controlled study.

BACKGROUND: Protamine administration post-cardiopulmonary bypass (CPB) can potentially cause hemodynamic instability. Histamine released from mast cells is believed to be responsible for hypotension after protamine administration. The aim of this study was to examine the effects of pretreatment with H1 and H2 antihistamines on changes in systemic arterial pressure following protamine administration. METHODS: This study was a randomized, triple-blinded, placebo-controlled study, conducted at a university hospital. Forty adult patients undergoing elective coronary artery bypass grafting (CABG) or single valve surgery were included. The patients were randomly allocated (20 patients in each group) to receive a single dose of combined chlorpheniramine 10 mg and ranitidine 50 mg or normal saline intravenously immediately after separation from CPB prior to protamine administration. Trajectory changes in systolic blood pressure (SBP), mean arterial pressure (MAP), and vasoactive-inotropic score (VIS) from baseline until 35 minutes following protamine administration (24-time points) were compared between the two groups. Serial serum tryptase levels were also obtained at baseline, 30 and 60 minutes after protamine was given. RESULTS: Forty patients were included in the analysis. Demographic and baseline blood pressure were similar between the two groups. At 30 minutes after protamine administration, there were no significant differences in both crude SBP [mean difference: -7.1 mmHg, 95% confidence interval (CI), -1.1 to 15.3 mmHg, P=0.09] and SBP after adjustment for the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), CPB time, and VIS (mean difference: -3.9 mmHg, 95% CI, -11.9 to 4.0 mmHg, P=0.33). There were also no significant differences in crude MAP (mean difference: -2.1 mmHg, 95% CI, -6.9 to 2.7 mmHg, P=0.39) and adjusted MAP (mean difference: -0.7 mmHg, -5.9 to 4.4 mmHg, P=0.78) between the two groups. None of the patients in both groups had a significant increase in serum tryptase from baseline. No differences in median serum tryptase levels at baseline, 30 and 60 minutes were demonstrated between the two groups. CONCLUSIONS: Pretreatment with H1 and H2 antihistamines does not attenuate blood pressure responses to protamine administration in patients after CPB. Mechanisms other than histamine release from mast cells might be responsible for protamine-induced cardiovascular changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03583567.