Estimated Cerebral Perfusion Pressure and Intracranial Pressure in Septic Patients.

BACKGROUND: Sepsis-associated brain dysfunction (SABD) is frequent and is associated with poor outcome. Changes in brain hemodynamics remain poorly described in this setting. The aim of this study was to investigate the alterations of cerebral perfusion pressure and intracranial pressure in a cohort of septic patients. METHODS: We conducted a retrospective analysis of prospectively collected data in septic adults admitted to our intensive care unit (ICU). We included patients in whom transcranial Doppler recording performed within 48 h from diagnosis of sepsis was available. Exclusion criteria were intracranial disease, known vascular stenosis, cardiac arrhythmias, pacemaker, mechanical cardiac support, severe hypotension, and severe hypocapnia or hypercapnia. SABD was clinically diagnosed by the attending physician, anytime during the ICU stay. Estimated cerebral perfusion pressure (eCPP) and estimated intracranial pressure (eICP) were calculated from the blood flow velocity of the middle cerebral artery and invasive arterial pressure using a previously validated formula. Normal eCPP was defined as eCPP ≥ 60 mm Hg, low eCPP was defined as eCPP < 60 mm Hg; normal eICP was defined as eICP ≤ 20 mm Hg, and high eICP was defined as eICP > 20 mm Hg. RESULTS: A total of 132 patients were included in the final analysis (71% male, median [interquartile range (IQR)] age was 64 [52-71] years, median [IQR] Acute Physiology and Chronic Health Evaluation II score on admission was 21 [15-28]). Sixty-nine (49%) patients developed SABD during the ICU stay, and 38 (29%) were dead at hospital discharge. Transcranial Doppler recording lasted 9 (IQR 7-12) min. Median (IQR) eCPP was 63 (58-71) mm Hg in the cohort; 44 of 132 (33%) patients had low eCPP. Median (IQR) eICP was 8 (4-13) mm Hg; five (4%) patients had high eICP. SABD occurrence and in-hospital mortality did not differ between patients with normal eCPP and patients with low eCPP or between patients with normal eICP and patients with high eICP. Eighty-six (65%) patients had normal eCPP and normal eICP, 41 (31%) patients had low eCPP and normal eICP, three (2%) patients had low eCPP and high eICP, and two (2%) patients had normal eCPP and high eICP; however, SABD occurrence and in-hospital mortality were not significantly different among these subgroups. CONCLUSIONS: Brain hemodynamics, in particular CPP, were altered in one third of critically ill septic patients at a steady state of monitoring performed early during the course of sepsis. However, these alterations were equally common in patients who developed or did not develop SABD during the ICU stay and in patients with favorable or unfavorable outcome.

Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management.

BACKGROUND: Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. METHODS: Retrospective analysis of prospectively collected data. INCLUSION CRITERIA: adult cardiac arrest survivors treated by targeted temperature management (TTM). EXCLUSION CRITERIA: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO). RESULTS: We included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. CONCLUSIONS: CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation.

BACKGROUND: Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. METHODS: Retrospective analysis of all patients undergoing venous-venous (V-V) or venous-arterial (V-A) ECMO with a concomitant EEG recording (April 2009-December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. RESULTS: A total of 139 patients (54 [41-62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno-arterial (V-A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25-16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24-82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. CONCLUSIONS: In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.

Multimodal non-invasive assessment of intracranial hypertension: an observational study.

BACKGROUND: Although placement of an intra-cerebral catheter remains the gold standard method for measuring intracranial pressure (ICP), several non-invasive techniques can provide useful estimates. The aim of this study was to compare the accuracy of four non-invasive methods to assess intracranial hypertension. METHODS: We reviewed prospectively collected data on adult intensive care unit (ICU) patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) in whom invasive ICP monitoring had been initiated and estimates had been simultaneously collected from the following non-invasive indices: optic nerve sheath diameter (ONSD), pulsatility index (PI), estimated ICP (eICP) using transcranial Doppler, and the neurological pupil index (NPI) measured using automated pupillometry. Intracranial hypertension was defined as an invasively measured ICP > 20 mmHg. RESULTS: We studied 100 patients (TBI = 30; SAH = 47; ICH = 23) with a median age of 52 years. The median invasively measured ICP was 17 [12-25] mmHg and intracranial hypertension was present in 37 patients. Median values from the non-invasive techniques were ONSD 5.2 [4.8-5.8] mm, PI 1.1 [0.9-1.4], eICP 21 [14-29] mmHg, and NPI 4.2 [3.8-4.6]. There was a significant correlation between all the non-invasive techniques and invasive ICP (ONSD, r = 0.54; PI, r = 0.50; eICP, r = 0.61; NPI, r = - 0.41-p < 0.001 for all). The area under the curve (AUC) to estimate intracranial hypertension was 0.78 [CIs = 0.68-0.88] for ONSD, 0.85 [95% CIs 0.77-0.93] for PI, 0.86 [95% CIs 0.77-0.93] for eICP, and 0.71 [95% CIs 0.60-0.82] for NPI. When the various techniques were combined, the highest AUC (0.91 [0.84-0.97]) was obtained with the combination of ONSD with eICP. CONCLUSIONS: Non-invasive techniques are correlated with ICP and have an acceptable accuracy to estimate intracranial hypertension. The multimodal combination of ONSD and eICP may increase the accuracy to estimate the occurrence of intracranial hypertension.

Comparison of 2 Automated Pupillometry Devices in Critically III Patients.

BACKGROUND: Automated pupillometry may help detect early cerebral disturbances in critically ill patients. It remains unclear whether different automated pupillometry devices can detect pupillary abnormalities with similar accuracy. The aim of this study was to compare the performance of 2 commercially available automated pupillometry devices-Neurolight Algiscan (NL) and NPi-200 (NP) versus standard pupillary light reflex (PLR) examination in an unselected cohort of critically ill patients. MATERIALS AND METHODS: This prospective study included all adult (>18 y) patients admitted to the intensive care unit of a university hospital over a 20-day period. Measurements were made consecutively with each method once during the intensive care unit stay in each patient. To assess sensitivity and specificity, we calculated areas under the curve of the receiver operating characteristic curve. RESULTS: A total of 112 patients were included in the study. There was a significant correlation between the 2 automated pupillometry devices for pupil size, constriction to light stimulation, and constriction velocity but not for pupillary latency. The mean bias for pupil size measured by the NL and the NP devices was -0.12 (limit of agreement [LoA], -1.29 to 1.06) mm, for pupil constriction -1.0% (LoA, -9.3% to 7.2%), and for latency 0.02 (LoA, -0.22 to 0.25) ms. There was a significant correlation between pupil size evaluated by clinical examination and that using the NL or NP. The areas under the curves for pupil constriction measured by NL and NP were 0.93 and 0.91, respectively, to detect clinically reactive pupils. CONCLUSIONS: Although there was a significant correlation between NL and NP values as well as with clinical examination of the PLR, the 2 devices were not always interchangeable, especially for the evaluation of pupillary latency.

Comparison of estimation of cardiac output using an uncalibrated pulse contour method and echocardiography during veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: During veno-venous extracorporeal membrane oxygenation, cardiac output monitoring is essential to assess tissue oxygen delivery. Adequate arterial oxygenation depends on the ratio between the extracorporeal pump blood flow and the cardiac output. The aim of this study was to compare estimates of cardiac output and blood flow/cardiac output ratios made using an uncalibrated pulse contour method with those made using echocardiography in patients treated with veno-venous extracorporeal membrane oxygenation. METHODS: Cardiac output was estimated simultaneously using a pulse contour method (MostCareUp; Vygon, Encouen, France) and echocardiography in 17 hemodynamically stable patients treated with veno-venous extracorporeal membrane oxygenation. Comparisons were made using Bland-Altman and linear regression analysis. RESULTS: There were significant correlations between cardiac output estimated using pulse contour method and echocardiography and between blood flow/cardiac output estimated using pulse contour method and blood flow/cardiac output estimated using echocardiography (r = 0.84, p < 0.001 and r = 0.87, p < 0.001, respectively). Bland-Altman analysis showed a good agreement (bias -0.20 ± 0.50 L/min) and a low percentage of error (25%) for the cardiac output values estimated by the two methods. The bias between the blood flow/cardiac output ratios obtained with the two methods was 5.19% ± 12.3% (percentage of error = 28.1%). CONCLUSIONS: The pulse contour method is a valuable alternative to echocardiography for the assessment of cardiac output and the blood flow/cardiac output ratio in patients treated with veno-venous extracorporeal membrane oxygenation.

Acute liver dysfunction after cardiac arrest.

Few data are available regarding hypoxic hepatitis (HH) and acute liver failure (ALF) in patients resuscitated from cardiac arrest (CA). The aim of this study was to describe the occurrence of these complications and their association with outcome. All adult patients admitted to the Department of Intensive Care following CA were considered for inclusion in this retrospective study. Exclusion criteria were early death (<24 hours) or missing biological data. We retrieved data concerning CA characteristics and markers of liver function. ALF was defined as a bilirubin >1.2 mg/dL and an international normalized ratio ≥1.5. HH was defined as an aminotransferase level >1000 IU/L. Neurological outcome was assessed at 3 months and an unfavourable neurological outcome was defined as a Cerebral Performance Categories (CPC) score of 3-5. A total of 374 patients (age 62 [52-74] years; 242 male) were included. ALF developed in 208 patients (56%) and HH in 27 (7%); 24 patients developed both conditions. Patients with HH had higher mortality (89% vs. 51% vs. 45%, respectively) and greater rates of unfavourable neurological outcome (93% vs. 60% vs. 59%, respectively) compared to those with ALF without HH (n = 184) and those without ALF or HH (n = 163; p = 0.03). Unwitnessed arrest, non-shockable initial rhythm, lack of bystander cardiopulmonary resuscitation, high adrenaline doses and the development of acute kidney injury were independent predictors of unfavourable neurological outcome; HH (OR: 16.276 [95% CIs: 2.625-81.345; p = 0.003), but not ALF, was also a significant risk-factor for unfavourable outcome. Although ALF occurs frequently after CA, HH is a rare complication. Only HH is significantly associated with poor neurological outcome in this setting.

Cerebral Near-Infrared Spectroscopy in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Acute cerebral complications (ACC) of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are associated with poor long-term neurologic outcome. We described the role of rSO2 monitoring in detecting ACC and desaturations and their relationship with poor outcome when employing VA-ECMO. METHODS: Retrospective analysis of patients monitored by cerebral frontal near-infrared spectroscopy (NIRS) (CAS Medical Systems Inc., Branford, CT, USA) during VA-ECMO (November 2008-December 2015). ACC was defined as the presence of stroke and/or brain death, while cerebral desaturation as cortical oxygen tissue saturation (rSO2) < 60%. RESULTS: Fifty-six of 159 VA-ECMO patients (age 55 [36-60] years) were included; 18 (32%) developed ACC and 36 died (64%). Cerebral desaturation occurred in 43 (74%) patients, who had a higher mortality than those without cerebral desaturation (74 vs. 31%). A high sequential organ failure assessment (SOFA) score on the first day of ECMO (OR 1.40 [95% CIs 1.06-1.84]) and the minimum ECMO blood flow during the first 4 days of therapy (OR 3.05 [1.01-9.17]) were independently associated with the occurrence of cerebral desaturation. Cerebral desaturation occurred more frequently in patients with ACC than others (94 vs. 68%); patients with ACC also had a lower minimal rSO2 over time (49 vs. 54%) and more frequently had high right-left rSO2 differences (33 vs. 8%), which were both independent predictors of ACC. The occurrence of cerebral desaturation (OR 7.93 [1.62-38.74]) and high lactate concentrations during the first 4 days of ECMO support (OR 1.22 [1.03-1.46]) was independently associated with hospital mortality. CONCLUSIONS: Monitoring of rSO2 could be considered as an interesting tool to monitor the brain of patients on VA-ECMO.

Altered liver function in patients undergoing veno-arterial extracorporeal membrane oxygenation (ECMO) therapy.

BACKGROUND: Multiple organ dysfunction can occur in patients undergoing Veno-arterial Extra Corporal Membrane Oxygenation (VA-ECMO); however, liver function has not been well studied in this setting. METHODS: In a review of our institutional ECMO database (n=162), we collected aspartate (AST) and alanine (ALT) transaminases, total bilirubin and international normalized ratio (INR) at time of ECMO initiation (baseline) and once daily during therapy in patients who survived for at least 24 hours. Elevated liver enzymes (ELE) were defined if AST and/or ALT were > 200 UI/L, and acute liver failure (ALF) as the presence of an INR ≥ 1.5, new onset encephalopathy and an elevated total bilirubin concentrations. RESULTS: On a total of 80 patients undergoing VA-ECMO, 69 patients met the inclusion criteria (cardiogenic shock, n=52; refractory cardiac arrest, n=15; cardiac failure following severe ARDS, n=2). Of them, 45 (65%) had early ELE after ECMO initiation (median highest AST and ALT were 528 [251-2606] UI/L and 513 [130-1031] UI/L, respectively). Two thirds of patients with ELE (N = 30) had a progressive reduction in AST and ALT, but the levels were normalized only after 5 [5-6] days. Among patients with ELE, 21/45 (47%) had AST and/or ALT levels above > 1000 UI/L. A total of 14/69 (20%) patients developed ALF. However, mortality rate was not significantly higher in patients with ELE or ALF when compared to others. CONCLUSIONS: A substantial proportion of patients needing VA-ECMO have early ELE, which usually improves over days. The prognostic implications are not evident.