Vasopressor Initiation Research Articles

Hemodynamic management of septic shock: beyond the Surviving Sepsis Campaign guidelines.

Although the Surviving Sepsis Campaign guidelines provide standardized and generalized guidance, they are less individualized. This review focuses on recent updates in the hemodynamic management of septic shock. Monitoring and intervention for septic shock should be personalized according to the phase of shock. In the salvage phase, fluid resuscitation and vasopressors should be given to provide life-saving tissue perfusion. During the optimization phase, tissue perfusion should be optimized. In the stabilization and de-escalation phases, minimal fluid infusion and safe fluid removal should be performed, respectively, while preserving organ perfusion. There is controversy surrounding the use of restrictive versus liberal fluid strategies after initial resuscitation. Fluid administration after initial resuscitation should depend upon the patient's fluid responsiveness and requires individualized management. A number of dynamic tests have been proposed to monitor fluid responsiveness, which can help clinicians decide whether to give fluid or not. The optimal timing for the initiation of vasopressor agents is unknown. Recent data suggest that early vasopressor initiation should be considered. Inotropes can be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion despite adequate volume status and arterial blood pressure. Venoarterial extracorporeal membrane oxygenation should be considered for refractory septic shock with severe cardiac systolic dysfunction.

What is new and different in the 2021 Surviving Sepsis Campaign guidelines.

The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult patients with (or at risk for) sepsis. This review discusses what is new or different in the 2021 SSC adult sepsis guidelines compared to 2016. The guidelines include new weak recommendations for use of balanced fluid over saline 0.9%, use of intravenous corticosteroids for septic shock when there is ongoing vasopressor requirement, and peripheral initiation of intravenous vasopressors over delaying initiation in order to obtain central venous access. As before, there is astrong recommendation to initiate antimicrobials within 1 h of sepsis and septic shock, but there are now additional recommendations when the diagnosis is uncertain. The recommendation for initial fluid resuscitation in septic shock of 30 mL/kg crystalloid has been downgraded from strong to weak. Finally, there are 12 new recommendations addressing long-term outcomes from sepsis, including strong recommendations to screen for economic and social support and to make referrals for follow-up where available; use shared decision-making in post-intensive care unit (ICU) and hospital discharge planning; reconcile medications at both ICU and hospital discharge; provide information about sepsis and its sequelae in written and verbal hospital discharge summary; and to provide assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge.

Lack of Association of Initial Vasopressor Dosing with Survival and Cardiac Re-Arrest Likelihood After Return of Spontaneous Circulation

BackgroundCardiac arrest occurs in approximately 350,000 patients outside the hospital and approximately 30,000 patients in the emergency department (ED) annually in the United States. When return of spontaneous circulation (ROSC) is achieved, hypotension is a common complication. However, optimal dosing of vasopressors is not clear. ObjectiveThe objective of this study was to determine if initial vasopressor dosing was associated with cardiac re-arrest in patients after ROSC. MethodsThis was a retrospective, single-center analysis of adult patients experiencing cardiac arrest prior to arrival or within the ED. Patients were assigned to one of four groups based on starting dose of vasopressor: low dose (LD; < 0.25 µg/kg/min), medium dose (MD; 0.25–0.49 µg/kg/min), high dose (HD; 0.5–0.99 µg/kg/min), and very high dose (VHD; ≥ 1 µg/kg/min). Data collection was performed primarily via manual chart review of medical records. The primary outcome was incidence of cardiac re-arrest within 1 h of vasopressor initiation. Multivariate logistic regression analysis was conducted to identify any covariates strongly associated with the primary outcome. ResultsNo difference in cardiac re-arrest incidence was noted between groups. The VHD group was significantly more likely to require a second vasopressor (p = 0.003). The HD group had lower survival rates to hospital discharge compared with the LD and MD groups (p = 0.0033 and p = 0.0147). In the multivariate regression, longer duration of pre-vasopressor re-arrests and hyperkalemic cardiac arrest etiology were significant predictors of cardiac re-arrest after vasopressor initiation. ConclusionsInitial vasopressor dosing was not found to be associated with risk of cardiac re-arrest or, conversely, risk of adverse events.

Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial

Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator. In this phase 2b trial, we aimed to confirm the hypothesis that TREM1 inhibition might improve outcomes in patients with septic shock. This double-blind, randomised, placebo-controlled, phase 2b trial assessed the efficacy and safety of two different doses of nangibotide compared with placebo, and aimed to identify the optimum treatment population, in patients across 42 hospitals with medical, surgical, or mixed intensive care units (ICUs) in seven countries. Non-COVID-19 patients (18-85 years) meeting the standard definition of septic shock, with documented or suspected infection (lung, abdominal, or urinary [in patients ≥65 years]), were eligible within 24 h of vasopressor initiation for the treatment of septic shock. Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3). Patients and investigators were masked to treatment allocation. Patients were grouped according to sTREM-1 concentrations at baseline (established from sepsis observational studies and from phase 2a change to data) into high sTREM-1 (≥ 400 pg/mL). The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population. Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response. This study is registered with EudraCT, 2018-004827-36, and Clinicaltrials.gov, NCT04055909. Between Nov 14, 2019, and April 11, 2022, of 402 patients screened, 355 were included in the main analysis (116 in the placebo group, 118 in the low-dose group, and 121 in the high-dose group). In the preliminary high sTREM-1 population (total 253 [71%] of 355; placebo 75 [65%] of 116; low-dose 90 [76%] of 118; high-dose 88 [73%] of 121), the mean difference in SOFA score from baseline to day 5 was 0·21 (95% CI -1·45 to 1·87, p=0·80) in the low-dose group and 1·39 (-0·28 to 3·06, p=0·104) in the high-dose group versus placebo. In the overall population, the difference in SOFA score from baseline to day 5 between the placebo group and low-dose group was 0·20 (-1·09 to 1·50; p=0·76),and between the placebo group and the high-dose group was 1·06 (-0·23 to 2·35, p=0·108). In the predefined high sTREM-1 cutoff population, 23 (31%) patients in the placebo group, 35 (39%) in the low-dose group, and 25 (28%) in the high-dose group had died by day 28. In the overall population, 29 (25%) patients in the placebo, 38 (32%) in the low-dose, and 30 (25%) in the high-dose group had died by day 28. The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups. High-dose nangibotide led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline. Low dose nangibotide displayed a similar pattern with lower magnitude of effect across all cutoff values. This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation. Inotrem.

Opportunities to improve diagnosis in emergency transfers to the pediatric intensive care unit.

Late recognition of in-hospital deterioration is a source of preventable harm. Emergency transfers (ET), when hospitalized patients require intensive care unit (ICU) interventions within 1 h of ICU transfer, are a proximal measure of late recognition associated with increased mortality and length of stay (LOS). To apply diagnostic process improvement frameworks to identify missed opportunities for improvement in diagnosis (MOID) in ETs and evaluate their association with outcomes. A single-center retrospective cohort study of ETs, January 2015 to June 2019. ET criteria include intubation, vasopressor initiation, or 60 mL/kg fluid resuscitation 1 h before to 1 h after ICU transfer. The primary exposure was the presence of MOID, determined using SaferDx. Cases were screened by an ICU and non-ICU physician. Final determinations were made by an interdisciplinary group. Diagnostic process improvement opportunities were identified. Primary outcomes were in-hospital mortality and posttransfer LOS, analyzed by multivariable regression adjusting for age, service, deterioration category, and pretransfer LOS. MOID was identified in 37 of 129 ETs (29%, 95% confidence interval [CI] 21%-37%). Cases with MOID differed in originating service, but not demographically. Recognizing the urgency of an identified condition was the most common diagnostic process opportunity. ET cases with MOID had higher odds of mortality (odds ratio 5.5; 95%CI 1.5-20.6; p = .01) and longer posttransfer LOS (rate ratio 1.7; 95%CI 1.1-2.6; p = .02). MOID are common in ETs and are associated with increased mortality risk and posttransfer LOS. Diagnostic improvement strategies should be leveraged to support earlier recognition of clinical deterioration.

Surviving Sepsis Campaign.

Surviving Sepsis Campaign.

Resuscitation in the First 3 Hours of Sepsis-Induced Hypotension Varies by Patient and Hospital Factors.

To evaluate variability in compliance to the 3-hour surviving sepsis campaign (SSC) bundle and explore the association of early compliance with subsequent shock and in-hospital mortality. Retrospective cohort study between September 2017 and February 2018. Thirty-four academic medical centers. A subgroup sepsis-induced hypotensive patients from a larger shock cohort study. Compliance to SSC bundle that was defined as receiving appropriate antibiotics, 30 mL/kg of crystalloid or initiation of vasopressors, and lactate, obtained in the first 3 hours following sepsis-induced hypotension. We included 977 patients with septic-induced hypotension. Bundle compliance was 43.8%, with the lowest compliance to fluid or vasopressor components (56%). Patients with high Sequential Organ Failure Assessment scores and physiologic assessments were more likely to receive compliant care, as were patients with sepsis-induced hypotension onset in the emergency department (ED) or admitted to mixed medical-surgical ICUs. SSC compliance was not associated with in-hospital mortality (adjusted odds ratio, 0.72; 95% CI, 0.47-1.10). The site-to-site variability contributed to SSC compliance (intraclass correlation coefficient [ICC], 0.15; 95% CI, 0.07-0.3) but not in-hospital mortality (ICC, 0.02; 95% CI, 0.001-0.24). Most patients remained in shock after 3 hours of resuscitation (SSC compliant 81.1% and noncompliant 53.7%). Mortality was higher among patients who were persistently hypotensive after 3 hours of resuscitation for both the SSC compliant (persistent hypotension 37% vs not hypotensive 27.2%; p = 0.094) and noncompliant (30.1% vs 18.2%; p = 0.001, respectively). Patients with a higher severity of illness and sepsis-induced hypotension identified in the ED were more likely to receive SSC-compliant care. SSC compliance was not associated with in-hospital mortality after adjusting for patient- and hospital-level differences. Higher mortality is seen among those who remain in shock after initial resuscitation, regardless of SSC compliance.

Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute Kidney Injury in Children With Shock: A Prospective Study.

The current definition of acute kidney injury (AKI) is based on serum creatinine (SrCr) and urine output, limited by delayed identification of such patients. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is considered an early diagnostic and highly predictive biomarker of AKI. To determine the diagnostic accuracy of NGAL for AKI compared with creatinine clearance for early detection of AKI in children with shock receiving inotropic support. Critically ill children requiring inotropic support in the pediatric intensive care unit were enrolled prospectively. SrCr and NGAL values were obtained three times at six, 12, and 48 hours after vasopressor initiation. Patients with AKI were defined as having loss of >25% renal function based on creatinine clearance within 48 hours. NGAL level of more than 150 ng/dl was suggestive of the diagnosis of AKI. Receiver operator characteristic curves were generated for NGAL and SrCr to compare the predictive ability of both at 0, 12, and 48 hours of starting vasopressor support. Results: A total of 94 patients were enrolled. The mean age was 43±50.95 months. Most common primary diagnoses were related to the cardiovascular system (46%). Twenty-nine patients (31%) died during the hospital stay. Thirty-four patients (36%) developed AKI within 48hours following shock. The area under the curve (AUC) for NGAL at a cutoff of 150 ng/ml was 0.70, 0.74, and 0.73 at six-hour, 12-hour, and 48-hour follow-up, respectively. NGAL had a sensitivity of 85.3% and specificity of 50% at 0 hours of follow-up for diagnosis of AKI. Serum NGAL has better sensitivity and AUC compared to SrCr for early diagnosis of AKI in children admitted with shock.

Early versus delayed vasopressor administration in patients with septic shock.

This study aimed to investigate the association of early vasopressor initiation with improved septic shock outcomes. This multicenter observational study was conducted in 17 intensive care units in Japan and included adult patients with sepsis admitted to the intensive care unit from July 2019 to August 2020 and treated with vasopressor therapy. Patients were divided into the early vasopressor group (≤1 h from sepsis recognition) and the delayed vasopressor group (>1 h). The impact of early vasopressor administration on risk-adjusted in-hospital mortality was estimated using logistic regression analyses adjusted by an inverse probability of treatment weighting analysis with propensity scoring. Among the 97 patients, 67 received vasopressor therapy within 1 h from sepsis recognition and 30 received vasopressor after 1 h. In-hospital mortality was 32.8% in the early vasopressor group and 26.7% in the delayed vasopressor group (p = 0.543). The adjusted odds ratio for in-hospital mortality was 0.76 (95% confidence interval 0.17-3.29) when comparing patients in the early vasopressor with those in the delayed vasopressor group. The fit curve from the mixed-effects model showed a relatively lower trend toward an infusion volume over time in the early vasopressor group than in the delayed vasopressor group. Our study did not reach a definitive conclusion for early vasopressor administration. However, early vasopressor administration may help avoid volume overload in the long course of sepsis care.

The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension

IntroductionPatients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. MethodsThis is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. ResultsScreening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). DiscussionCardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability.

1183: USE OF PERIPHERAL VASOPRESSORS IN EARLY SEPSIS-INDUCED HYPOTENSION ACROSS MICHIGAN HOSPITALS

Introduction: Recent data suggest it may be safe to administer vasopressors via peripheral IV (PIV), challenging convention that vasopressors must be delivered centrally. Surviving Sepsis Campaign 2021 guidelines suggest using peripheral vasopressors as a bridge to central access. However, little is known about vasopressor initiation in practice. Methods: Cohort study of patients hospitalized with community-onset sepsis at 12 hospitals in the Hospital Medicine Safety Consortium (HMS) sepsis initiative. HMS is a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan. A random sample of adult sepsis hospitalizations between 11/2020-1/2022 were included. Data were abstracted by trained abstractors. We sought to determine how commonly vasopressors were initiated via PIV vs central access across hospitals. HMS-Sepsis is expanding to 69 hospitals. Here we present pilot data; full cohort analysis is in process. Results: Of 1,901 patients in the HMS-Sepsis registry at the time of pilot data analysis, 440 (23.1%) had hypotension (defined by mean arterial pressure< 65mmHg, systolic blood pressure< 90mmHg, and/or vasopressor initiation) within 3 hours of hospital arrival. Of these, 160 (36.4%) received vasopressors within 6 hours of hospital arrival. Route of initial vasopressor was PIV in 122 (76.3%), central access in 30 (18.8%), midline catheter in 1 (0.6%), oral (ie, midodrine) in 5 (3.1%), and unknown in 2 (1.3%). Across all hospitals, 50.0% to 91.7% of vasopressor initiation was via PIV (median 83.3%). Among 122 patients with vasopressor initiation via PIV, 66 (54.1%) received a 2nd vasopressor, after a median of 2.8 hrs [IQR 1, 8] from 1st vasopressor. Route of 2nd vasopressor was PIV in 27 (40.9%) and central access in 30 (45.4%). Time from hypotension to vasopressor initiation did not differ between patients receiving initial vasopressor via PIV vs central access (median 1.9 vs 2.1 hrs, p=0.79). Likewise, IV fluids within 6 hrs (median 2.0 vs 2.1L, p=0.78), hospitalization length (median 7 vs 6 days, p=0.31), and in-hospital mortality (33.6% vs 40.0%, p=0.51) were similar. Conclusions: In this 12-hospital cohort, vasopressors were most frequently initiated peripherally. Outcomes were similar between patients in whom vasopressors were initiated via peripheral vs central access.

815: TIME TO HEMODYNAMIC STABILITY AFTER IMPLEMENTATION OF A NOREPINEPHRINE RAPID TITRATION PROTOCOL

Introduction: Norepinephrine (NE) is the primary vasoactive medication for many different shock states and is titrated to have a hemodynamic effect. A rapid titration protocol was recently implemented at our institution to provide nurses the ability to quickly titrate NE and comply with Joint Commission regulations. The purpose of this study is to evaluate whether implementing a rapid titration protocol for NE impacted time to hemodynamic stability in critically ill patients. Methods: A single-center, retrospective study of adult ICU patients receiving NE as a first line agent at a large academic medical center was performed. The patients were categorized into the pre-implementation group with standard titration instructions from April 2022 and the post implementation group with the rapid titration instructions from July 2022. Our primary outcome was to evaluate the time to hemodynamic stability based on mean arterial pressure (MAP) goals. Secondary outcomes included ICU and hospital length of stay (LOS), all-cause mortality and safety outcomes with NE administration. Results: A total of 64 patients were included in our analysis, of which, 30 patients were included in the pre-implementation group and 34 in the post-implementation group. Baseline characteristics were similar in both the groups, including NE starting rate (0.07 mcg/kg/min vs 0.08 mcg/kg/min, p=0.9), and Modified Early Warning Score (5 vs. 4, p=0.07). The primary outcome of time to hemodynamic stability based on MAP did not differ between the groups (median 12.5 minutes [IQR 0-28] vs. 11.5 minutes [IQR 0-36], p=0.7). However, the rapid titration group received significantly less concomitant IV vasopressors in the first 24 hours (50% vs. 18%, p=0.006) and experienced longer time to second vasopressor initiation (median 2.5 hours [IQR 0.10-3.6] vs. 10 hours [IQR 2.5-20]). Conclusions: At our institution, rapid titration instructions for NE did not shorten time to hemodynamic stability compared to the standard titration protocol. Our study shows that utilizing the NE rapid titration protocol may be safe and may reduce the need for an additional vasopressor. Further prospective studies are warranted to assess compliance with implementing a rapid titration protocol and its potential benefits.

1152: USE OF POINT-OF-CARE ULTRASOUND IN EVALUATING UNSTABLE PATIENTS OUTSIDE INTENSIVE CARE UNITS

Introduction: Point of care ultrasound (POCUS) has become an integral asset in intensive care units (ICU). However, there is limited literature on the value of POCUS in evaluating deteriorating patients outside ICU. In this study, we sought to investigate the use and impact of POCUS by ICU triage teams in hospitals outside of the ICU. Methods: For consults and rapid responses, ICU fellows were provided a portable ultrasound to use as part of their patient evaluations. Fellows were asked to fill out a survey regarding how ultrasound was used and its impact on patient management. Free text data such as reason for ultrasound use, views obtained, clinical impressions before and after ultrasound as well as how clinical decisions changed were recorded. These data were transcribed and categorized electronically, and then analyzed via Stata. Results: 51 total resuscitations were documented. The most common reason for ICU triage team evaluation was hypotension (53%). The most common clinical focus for ultrasound usage was volume status assessment (35%), followed by cardiac assessment (31%) and then pulmonary embolism evaluation (14%). Most common ultrasound views obtained were parasternal long (82%), followed by apical 4 chamber (76%) and subcostal views (75%). 79% of pre-ultrasound clinical impressions were confirmed by ultrasound use. However, when assessing for pulmonary embolisms, 40% of clinical impressions changed after using ultrasound. 37% of encounters had a significant clinical action taken based on ultrasound findings (fluid resuscitation, vasopressor initiation, etc), which increased to 50% when specifically evaluating cardiac assessment and volume status. Conclusions: Ultrasound is a valuable tool in patient evaluation on non-ICU wards especially in confirming clinical impressions and guiding therapeutic actions. Some limitations of this study include reporting bias and incomplete capture of all ultrasound usage on non-ICU wards. Next steps will include further analysis on specific presenting complaints (i.e mental status change, hypotension, dyspnea) and outcomes based on ultrasound usage outside the ICU.

728: OUTCOMES AND TIMING OF STRESS-DOSE HYDROCORTISONE IN PEDIATRIC SEPTIC SHOCK

Introduction: Sepsis is a major contributor to pediatric morbidity and mortality worldwide. Pediatric sepsis is defined as systemic inflammatory response syndrome (SIRS) in the presence of suspected or confirmed infection. Pediatric septic shock is defined as sepsis with cardiovascular organ dysfunction. In vasoactive-inotropic recalcitrant septic shock, stress dose corticosteroids are often administered for presumed critical illness related corticosteroid insufficiency (CIRCI). However, there is not consistent data to support the use of stress dose hydrocortisone (HCT) in septic shock. To further investigate clinical outcomes related to timing of HCT, we hypothesized that children with vasoactive-inotropic recalcitrant septic shock who received early HCT (< 6 hours) would have lower vasoactive-inotropic scores (VIS) in the first 48 hours, a decreased length of stay (LOS) and increased ventilator-free days (VFD). Methods: A retrospective chart review was performed from November 2017 to December 2021 of subjects 0 to < 18 years, admitted to the pediatric intensive care unit (PICU) meeting the definition for septic shock, requiring vasopressors and/or inotropes and given HCT for CIRCI. We measured VIS, PICU and hospital LOS and VFD. Subjects with chronic steroid use or who received etomidate were excluded. Results: Of 227 subjects screened, 23 met criteria for analysis. Seven subjects received HCT within 6 hours of vasopressor initiation (early group), while 16 received HCT >6 hours (late group). Initial VIS average was 10.96 in the early group and 10.78 in the late group. At 48 hours, average VIS in the early group was 9.51 and 1.44 in the late group. Average PICU LOS was 15.58 for the early group and 10.82 for the late group. Average hospital LOS was 37.47 for the early group and 19.76 for the late group. VFD average was 15.32 in the early group and 16.61 in the late group. Pediatric Index of Mortality 3 (PIM-3) average in the early group was 2.02 and 1.61 in the late group. Mortality incidence was 2 in 7 in the early group, and 4 in 16 in the late group. Conclusions: Preliminary data suggests there is an increased VIS at 48 hours, increased PICU and hospital LOS, and decreased VFD with early administration of HCT. Although PIM-3 scores were higher in the early group, mortality was similar between groups.

1219: EFFECT OF HIGH-DOSE THIAMINE INJECTION ON SHOCK REVERSAL IN SEPTIC PATIENTS

Introduction: Thiamine (TH) is a co-factor for pyruvate dehydrogenase, an enzyme necessary for pyruvate entry into the Krebs cycle, and without this enzyme, pyruvate would be converted to lactate. Elevated lactate, which is often used as a marker of perfusion, is proportionally associated with increased mortality in septic shock. The few publications on TH in septic shock are inconclusive. This study aims to ascertain if there is benefit to adding TH to standard of care (SOC) in the management of septic shock. Methods: IRB-approved, multicenter, retrospective review from 2016 to 2021. Adult patients admitted to the ICU for septic shock and receiving ≥ 400 mg a day of IV TH (in divided doses) were included. Patients < 18, pregnant, admitted for SARS-COV-2, or whom received < 400 mg of TH daily were excluded. Two matched cohorts were evaluated, SOC plus TH versus SOC alone. The primary endpoint is time to shock reversal, defined as off vasopressors for at least 12 hrs and alive. Secondary endpoints include time to lactate clearance (< 2 mmol/L), lactate trends at 6, 12, 24, 48 hrs, and end of therapy, hospital and ICU lengths of stay, new end organ dysfunction, and in-hospital mortality. Results: Data from 50 patients were analyzed: 25 in the SOC plus TH and 25 in the SOC arm. The TH arm had greater number of vasopressors (2 vs. 1, p=.019), and greater utilization of stress-dose steroids (72% vs. 8%, p<.001), however there was no difference in cumulative vasopressor dose in norepinephrine equivalents at baseline (BL) (30.1 vs. 25.8 mcg/min, p=.248). There was no difference in SOFA score at ICU admission (10 vs. 8.5, p=.106) or lactate level at ICU admission (5.9 vs. 3.9 mmol/L, p=.055). There was a longer time to shock reversal from vasopressor initiation time in the TH arm (93 vs. 37.1 hrs, p=.023). Lactate clearance was slower in the TH arm (44.75 vs. 15.8 hrs, p=.027), and there was increased in-hospital mortality in the TH arm (13 vs. 5, p=.018). Conclusions: Compared to SOC alone, TH treated patients had longer times to shock reversal. However, this outcome may have been confounded by differences at BL with regard to number of vasopressors, and stress-dose steroid utilization, which indicate these patients were sicker at BL. Larger, prospective studies are required to confirm these findings.

Dopamine versus norepinephrine as the first-line vasopressor in the treatment of cardiogenic shock.

Only a few observational studies using small patient samples and one subgroup analysis have compared norepinephrine and dopamine for the treatment of cardiogenic shock (CS). The objective of the present study was to investigate whether the use of norepinephrine was associated with improvements in clinical outcomes in CS patients compared to dopamine. We retrospectively reviewed hospital medical records of patients who were admitted to cardiac intensive care unit from 2012 to 2018. We included 520 patients with CS in this analysis. The primary outcome was in-hospital mortality, and serial hemodynamic data were also assessed. As a first-line vasopressor, dopamine was used in 156 patients (30%) and norepinephrine in 364 patients (70%). Overall, the norepinephrine group had significantly higher severity of shock, arrest at presentation, vital signs, and lactic acid than did the dopamine group at the time of vasopressor initiation. Nevertheless, in the norepinephrine group, additional vasopressor was required in 123 patients (33.8%), which was a significantly smaller percentage than the 92 patients (56.4%) in the dopamine group who required additional vasopressor (p < 0.001). There was no significant difference in in-hospital mortality between the two groups (26.9% and 31.9%, respectively, p = 0.26). In addition, the incidence of arrhythmia was not different between the two groups (atrial fibrillation, 12.2% vs. 15.7%, p = 0.30; ventricular tachyarrhythmia, 19.9% vs. 25.3%, p = 0.18). The use of norepinephrine as a first-line vasopressor was not associated with reductions of in-hospital mortality or arrythmia but could reduce use of additional vasopressors in CS patients.

Feasibility of Very Early Identification of Cardiogenic Shock by Semi-automated Ultrasound Exam in the Emergency Department.

Background Cardiogenic shock (CS) is critical end-organ hypoperfusion due to reduced cardiac output. Early therapy, such as vasoactive agents or the initiation of mechanical circulatory support (MCS), requires early diagnosis and is associated with better outcomes. A novel ultrasound platform (GE Healthcare, Milwaukee, WI) has semi-automated imaging software (SAIS), which could simplify the point-of-care ultrasound (POCUS) diagnosis of CS. We assessed the feasibility of using POCUS with SAIS in patients in shock, determined the ability of SAIS to identify the subset of patients with CS, and described the process and outcome of care of patients with vs. without CS after presenting to Emergency Department (ED) with hypotension. Methods This prospective case-control study was conducted at an urban ED. Physicians with prior POCUS education received one hour of training with the study device. The qualitative ejection fraction was determined by visual assessment. SAIS measurements of hemodynamics were made with the study device and included left ventricle outflow tract velocity time integral (LVOT VTI), inferior vena cava collapsibility or distensibility indices, and pulmonary B-line assessment.ED patients with a systolic blood pressure ≤ 90 mmHg or need for a vasopressor initiation in the ED were enrolled. The diagnosis of CS was determined by a medical record review. All data were summarized descriptively. Results Twenty-ninecases underwent POCUS, and 87 controls did not. Baseline characteristics, process, and outcome of care were similar between groups. Seventy-nine percent (79%) of cases had a complete POCUS with SAIS. Of these, 55% had reduced LVOT VTI, 38% had IVC collapsibility <50%, and 48% of cases had a B-line pattern consistent with pulmonary edema. The mean LVOT VTI for cases with CS was 9.4± 5.4 cm; the mean LVOT VTI for cases without CS was 15.2 ± 6.0 cm. Among patients who did not undergo POCUS, 31 (36%) had a formal echocardiogram, and eight (9%) had a final diagnosis of cardiogenic shock during hospitalization. Conclusion Physicians with one hour of platform-specific training were able to implement POCUS with SAIS among patients who present with shock. POCUS with SAIS may aid in the early recognition of CS.

Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57-0.96) or Asian (OR, 0.6; 95% CrI, 0.35-0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.

Alterations in tissue oxygen saturation measured by near-infrared spectroscopy in trauma patients after initial resuscitation are associated with occult shock

PurposePersistent occult hypoperfusion after initial resuscitation is strongly associated with increased morbidity and mortality after severe trauma. The objective of this study was to analyze regional tissue oxygenation, along with other global markers, as potential detectors of occult shock in otherwise hemodynamically stable trauma patients.MethodsTrauma patients undergoing active resuscitation were evaluated 8 h after hospital admission with the measurement of several global and local hemodynamic/metabolic parameters. Apparently hemodynamically stable (AHD) patients, defined as having SBP ≥ 90 mmHg, HR < 100 bpm and no vasopressor support, were followed for 48 h, and finally classified according to the need for further treatment for persistent bleeding (defined as requiring additional red blood cell transfusion), initiation of vasopressors and/or bleeding control with surgery and/or angioembolization. Patients were labeled as “Occult shock” (OS) if they required any intervention or “Truly hemodynamically stable” (THD) if they did not. Regional tissue oxygenation (rSO2) was measured non-invasively by near-infrared spectroscopy (NIRS) on the forearm. A vascular occlusion test was performed, allowing a 3-min deoxygenation period and a reoxygenation period following occlusion release. Minimal rSO2 (rSO2min), Delta-down (rSO2–rSO2min), maximal rSO2 following cuff-release (rSO2max), and Delta-up (rSO2max–rSO2min) were computed. The NIRS response to the occlusion test was also measured in a control group of healthy volunteers.ResultsSixty-six consecutive trauma patients were included. After 8 h, 17 patients were classified as AHD, of whom five were finally considered to have OS and 12 THD. No hemodynamic, metabolic or coagulopathic differences were observed between the two groups, while NIRS-derived parameters showed statistically significant differences in Delta-down, rSO2min, and Delta-up.ConclusionsAfter 8 h of care, NIRS evaluation with an occlusion test is helpful for identifying occult shock in apparently hemodynamically stable patients.Level of evidenceIV, descriptive observational study.Trial registrationClinicalTrials.gov Registration Number: NCT02772653.

Use of peripherally inserted central catheters with a dedicated vascular access specialists team versus centrally inserted central catheters in the management of septic shock patients in the ICU.

Peripherally inserted central catheters (PICCs) are increasingly recognized as an alternative to centrally inserted central catheters (CICCs) in critical care, yet the data regarding the safety and feasibility of this choice in septic shock management is growing but still lacking. In this study, we aimed to determine the feasibility, safety, and impact on outcomes of using dedicated vascular access specialist (VAS) teams to insert PICCs versus CICCs on patients admitted to the ICU with septic shock. Retrospective cohort study. Mayo Clinic Rochester Medical ICU and Mayo Clinic Arizona Multidisciplinary ICU from 2013 to 2016. All adult patients hospitalized with diagnosis of septic shock excluding patients who declined authorization for review of their medical records, mixed shock states, and readmissions. None. Comprehensive data regarding septic shock diagnosis and resuscitation were abstracted from electronic medical records. A total of 562 patients with septic shock were included in the study; 215 patients were resuscitated utilizing a PICC and 347 were resuscitated using a CICC. On univariate analysis, the time to central line insertion and time to vasopressor initiation were found to be reduced in those who received PICC at time of ICU admission versus CICC. Other favorable outcomes were also observed in those who received PICC versus CICC including shorter ICU length of stay and lower unadjusted hospital mortality. A multivariable analysis for hospital mortality showed that after adjusting for important covariates, neither the time to central line insertion nor the time to vasopressor initiation was associated with a lower hospital mortality. Across two tertiary referral centers within the same enterprise, use of a dedicated VAS team for insertion of PICCs for initial resuscitation in patients with septic shock was feasible and associated with shorter time to central venous access and initiation of vasopressors; however, adjusted hospital mortality was not different between the two groups.