Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. METHODS: This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. RESULTS: Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57-69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51-54]% vs. 49 [47-50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56-71] to 82 [76-87] mmHg, p = 0.005) and rSO2 (from 53 [52-54]% to 60 [59-64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67-73] to 72 [67-73] mmHg, p = 0.015) and rSO2 (from 53 [51-56]% to 57 [55-59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75-79] to 64 [60-70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56-65]% vs. 56 [53-62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). CONCLUSIONS: Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).

Effects of institutional caseload of subarachnoid hemorrhage on mortality: a secondary analysis of administrative data.

BACKGROUND AND PURPOSE: Procedures requiring specific skill sets often have been shown to depend on institutional volume, that is, centers receiving a higher volume observe better outcomes in those patients. This relationship recently has been shown to exist for subarachnoid hemorrhage(SAH) patients in a large study in the United States. We aim to examine this relationship for SAH patients in England, restricting analysis to specialist neurosurgical units. METHODS: Aggregate counts of patients with SAH in 25 specialist neuroscience centers in England, from 2005 to 2011, were obtained from the Hospital Episode Statistics database maintained by the National Health Service Information Center. These data were linked with national mortality statistics to obtain counts of deaths. Poisson regression was used to investigate the relationship between institutional caseload of SAH and 6-month mortality from any cause. Six-month mortality rates and mortality ratios were computed. RESULTS: Annual institutional caseload of admissions with SAH was inversely related to 6-month mortality (P=0.009; r(2)=0.26). Each 100-patient increase in annual patient volume was associated with a 24% reduction in mortality (adjusted mortality ratio, 0.76; confidence interval, 0.67-0.87). This relationship was consistent across the entire range of annual institutional caseloads examined (29-367 cases for the lowest and highest volumes seen in a single center in 1 year). CONCLUSIONS: Our results provide support for management of SAH at high-volume centers and suggest that health care policy in this setting should pursue regionalization while ensuring an adequate geographic spread of access to care.

The role of noninvasive brain oximetry in adult critically ill patients without primary non-anoxic brain injury.

A primary objective in intensive care and perioperative settings is to promote an adequate supply and delivery of oxygen to tissues and organs, particularly to the brain. Cerebral near infrared spectroscopy (NIRS) is a noninvasive, continuous monitoring technique, that can be used to assess cerebral oxygenation. Using NIRS to monitor cerebral oximetry is not new and has been in widespread use in neonates and cardiac surgery for decades. In addition, it has become common to see NIRS being used in adult and pediatric cardiac surgery, acute neurological diseases, neurosurgical procedures, vascular surgery, severe trauma and other acute medical diseases. Furthermore, recent evidence suggests a role for NIRS in the perioperative settings; detecting and preventing episodes of cerebral desaturation aiming to reduce the development of postoperative delirium. NIRS is not without its limitations; these include the risk of extra-cranial contamination, spatial limitations and skin blood flow/volume changes, as well being a measure of localized blood oxygenation underneath the sensor. However, NIRS is a noninvasive technique and can be used in those patients without indications or justification for invasive brain monitoring; non-neurosurgical procedures such as liver transplantation, major orthopedic surgery and critically illness where the brain is at risk. The aim of this manuscript was to discuss the physical principles of NIRS and to report the current evidence regarding its use in critically ill patients without primary non-anoxic brain injury.

Early Effects of Passive Leg-Raising Test, Fluid Challenge, and Norepinephrine on Cerebral Autoregulation and Oxygenation in COVID-19 Critically Ill Patients.

Background: Coronavirus disease 2019 (COVID-19) patients are at high risk of neurological complications consequent to several factors including persistent hypotension. There is a paucity of data on the effects of therapeutic interventions designed to optimize systemic hemodynamics on cerebral autoregulation (CA) in this group of patients. Methods: Single-center, observational prospective study conducted at San Martino Policlinico Hospital, Genoa, Italy, from October 1 to December 15, 2020. Mechanically ventilated COVID-19 patients, who had at least one episode of hypotension and received a passive leg raising (PLR) test, were included. They were then treated with fluid challenge (FC) and/or norepinephrine (NE), according to patients' clinical conditions, at different moments. The primary outcome was to assess the early effects of PLR test and of FC and NE [when clinically indicated to maintain adequate mean arterial pressure (MAP)] on CA (CA index) measured by transcranial Doppler (TCD). Secondary outcomes were to evaluate the effects of PLR test, FC, and NE on systemic hemodynamic variables, cerebral oxygenation (rSo2), and non-invasive intracranial pressure (nICP). Results: Twenty-three patients were included and underwent PLR test. Of these, 22 patients received FC and 14 were treated with NE. The median age was 62 years (interquartile range = 57-68.5 years), and 78% were male. PLR test led to a low CA index [58% (44-76.3%)]. FC and NE administration resulted in a CA index of 90.8% (74.2-100%) and 100% (100-100%), respectively. After PLR test, nICP based on pulsatility index and nICP based on flow velocity diastolic formula was increased [18.6 (17.7-19.6) vs. 19.3 (18.2-19.8) mm Hg, p = 0.009, and 12.9 (8.5-18) vs. 15 (10.5-19.7) mm Hg, p = 0.001, respectively]. PLR test, FC, and NE resulted in a significant increase in MAP and rSo2. Conclusions: In mechanically ventilated severe COVID-19 patients, PLR test adversely affects CA. An individualized strategy aimed at assessing both the hemodynamic and cerebral needs is warranted in patients at high risk of neurological complications.

Hypertonic saline in patients with poor-grade subarachnoid hemorrhage improves cerebral blood flow, brain tissue oxygen, and pH.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia and infarction due to reduced CBF remains the leading cause of poor outcome after aneurysmal subarachnoid hemorrhage. Hypertonic saline (HS) is associated with an increase in CBF. This study explores whether CBF enhancement with HS in patients with poor-grade subarachnoid hemorrhage is associated with improved cerebral tissue oxygenation. METHODS: Continuous monitoring of arterial blood pressure, intracranial pressure, cerebral perfusion pressure, brain tissue oxygen, carbon dioxide, pH, and middle cerebral artery flow velocity was performed in 44 patients. Patients were given an infusion (2 mL/kg) of 23.5% HS. In 16 patients, xenon CT scanning was also performed. CBF in a region surrounding the tissue oxygen sensor was calculated. Data are mean+/-SD. RESULTS: Thirty minutes postinfusion, a significant increase in arterial blood pressure, cerebral perfusion pressure, flow velocity, brain tissue pH, and brain tissue oxygen was seen together with a decrease in intracranial pressure (P<0.05). Intracranial pressure remained reduced for >300 minutes and flow velocity elevated for >240 minutes. A significant increase in brain tissue oxygen persisted for 240 minutes. Average baseline regional CBF was 33.9+/-13.5 mL/100 g/min, rising by 20.3%+/-37.4% (P<0.05) after HS. Patients with favorable outcome responded better to HS in terms of increased CBF, brain tissue oxygen, and pH and reduced intracranial pressure compared with those with an unfavorable outcome. A sustained increase in brain tissue oxygen (beyond 210 minutes) was associated with favorable outcome (P<0.023). CONCLUSIONS: HS augments CBF in patients with poor-grade subarachnoid hemorrhage and significantly improves cerebral oxygenation for 4 hours postinfusion. Favorable outcome is associated with an improvement in brain tissue oxygen beyond 210 minutes.

Serum albumin level as a predictor of outcome in traumatic brain injury: potential for treatment.

BACKGROUND: Serum albumin level is correlated with outcome in various clinical situations. Albumin has multiple physiologic properties that could be beneficial in brain injury. The Lund therapy for elevated intracranial pressure uses albumin as part of its protocol and demonstrates favorable outcome. We sought to find out if albumin is associated with outcome after traumatic brain injury to justify conducting a randomized trial. METHODS: A retrospective study of traumatic brain injury patients was conducted. Characteristics known to influence outcome were included in a multiple logistic regression model to analyze predictors of poor outcome at 6 months. RESULTS: Data were available for 138 patients. The majority of patients (65%) had a severe injury (Glasgow Coma Scale score <9). Seventy percent of patients had a favorable outcome. Albumin levels decrease considerably from normal values in the first few days after injury irrespective of outcome. Albumin remained <25 g/L for a longer period of time in patient with an unfavorable outcome (6 days vs. 3 days, p = 0.012). Multiple logistic regression analysis identified albumin levels, age, Glasgow Coma Scale score at admission, and Injury Severity Score as predictors of poor outcome. CONCLUSION: Serum albumin level seems to be an independent predictor of poor outcome. The model also identified classic predictors of poor outcome that tends to strengthen its adequacy. Because albumin level is the only modifiable factor influencing outcome, it seems justified to carry out a randomized trial of the use of albumin in the treatment of brain injury.

Hyperglycaemia and neurological injury.

PURPOSE OF REVIEW: Clinical and experimental data suggest that hypergylcaemia lowers the ischaemic neuronal threshold and worsens outcome in the presence of neurological injury from trauma, stroke and subarachnoid haemorrhage. This review aims to appraise the evidence for tight glycaemic control in patients with neurological injury. RECENT FINDINGS: Hyperglycaemia can adversely affect outcome in critically ill patients. Intensive insulin therapy with tight glycaemic control has been advocated for improving outcome in these patients. However, the extent to which intensive insulin therapy and tight control of blood glucose improve outcome after ischaemic neurological insults remains unclear. The benefit of such treatment regimes may be negated by the increased frequency of hypoglycaemic episodes, which may aggravate neurological injury. Although it seems sensible to control hyperglycaemia in patients with neurological injury, the treatment must account for potential hypoglycaemic episodes. SUMMARY: Clinical and experimental data suggest that hyperglycaemia lowers the ischaemic neuronal threshold in the presence of neurological injury. Tight glycaemic control may result in hypoglycaemia, which in itself can be detrimental. Therefore, it seems sensible that we should accept slightly less tight blood glucose control than in the critically ill patient without neurological injury.

Extracorporeal membrane oxygenation for adult respiratory distress syndrome in trauma patients: A case series and systematic literature review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an established salvage therapy for severe respiratory failure, and may provide an alternative form of treatment for trauma-induced adult respiratory distress syndrome (ARDS) when conventional treatments have failed. The need for systemic anticoagulation is a relative contraindication for patients with bleeding risks, especially in multitraumatic injury. METHODS: We describe a case series of four trauma patients with ARDS who were managed with ECMO admitted to the neuro critical care unit at Addenbrooke's Hospital, Cambridge (UK), from January 2000 to January 2016. We performed a systematic review of the available literature to investigate the safety and efficacy of vv-ECMO in posttraumatic ARDS, focusing on the use of different anticoagulation strategies and risk of bleeding on patients with multiple injuries. RESULTS: Thirty-one patients were included. A heparin bolus was given in 16 cases. Eleven patients developed complications during treatment with ECMO with three cases of major bleeding. In all documented cases of bleeding a bolus and infusion of heparin was administered, aiming for an activated clotting time (ACT) target longer than 150 seconds. Two patients treated with heparin-free ECMO developed thromboembolic complications. Four patients died, and death was never directly or indirectly related to use of ECMO. CONCLUSION: vv-ECMO can be lifesaving in respiratory failure. Our experience and our literature review suggest that vv-ECMO should be considered as a rescue treatment for the management of severe hypoxemic respiratory failure secondary to ARDS in trauma patients.For patients with a high risk of bleeding, the use of ECMO with no initial anticoagulation could be considered a valid option. For patients with a moderate risk of bleeding, use of a heparin infusion keeping an ACT target shorter than 150 seconds can be appropriate. LEVEL OF EVIDENCE: Therapeutic study, level V.

Asymmetry of pressure autoregulation after traumatic brain injury.

OBJECT: The aim of this study was to assess the asymmetry of autoregulation between the left and right sides of the brain by using bilateral transcranial Doppler ultrasonography in a cohort of patients with head injuries. METHODS: Ninety-six patients with head injuries comprised the study population. All significant intracranial mass lesions were promptly removed. The patients were given medications to induce sedation and paralysis, and artificial ventilation. Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in an invasive manner. A strategy based on the patient's cerebral perfusion pressure (CPP = ABP - ICP) was applied: CPP was maintained at a level higher than 70 mm Hg and ICP at a level lower than 25 mm Hg. The left and right middle cerebral arteries were insonated daily, and bilateral flow velocities (FVs) were recorded. The correlation coefficient between the CPP and FV, termed Mx, was calculated and time-averaged over each recording period on both sides. An Mx close to 1 signified that slow fluctuations in CPP produced synchronized slow changes in FV, indicating a defective autoregulation. An Mx close to 0 indicated preserved autoregulation. Computerized tomography scans in all patients were reviewed; the side on which the major brain lesion was located was noted and the extent of the midline shift was determined. Outcome was measured 6 months after discharge. The left-right difference in the Mx between the hemispheres was significantly higher in patients who died than in those who survived (0.16 +/- 0.04 compared with 0.08 +/- 0.01; p = 0.04). The left-right difference in the Mx was correlated with a midline shift (r = -0.42; p = 0.03). Autoregulation was worse on the side of the brain where the lesion was located (p < 0.035). CONCLUSIONS: The left-right difference in autoregulation is significantly associated with a fatal outcome. Autoregulation in the brain is worse on the side ipsilateral to the lesion and on the side of expansion in cases in which there is a midline shift.

Symmetry of cerebral hemodynamic indices derived from bilateral transcranial Doppler.

OBJECTIVE: The authors evaluated with bilateral transcranial Doppler (TCD) ultrasonography the norm of interhemispheric difference for several cerebrovascular hemodynamic parameters. METHODS: Forty-four volunteers (33 male, 11 female; average age = 21 years; range, 20-23 years) were studied. The authors recorded bilateral systolic, diastolic, and mean flow velocity (FV) and noninvasive systolic, diastolic, and mean arterial blood pressure. Calculated indices included Gosling's pulsatility index (GPI), an index of autoregulation (Mx), critical closing pressure (CCP), and a noninvasive estimator of cerebral perfusion pressure (nCPP). All indices were averaged per side and patient. For each parameter, the left-right correlation coefficient (r2) and the 95% confidence limit of the left-right differences were calculated. RESULTS: All TCD-derived indices displayed significant correlations between the left and right sides: r2 = 0.49 for mean FV (FVm), r2 = 0.66 for GPI, r2 = 0.79 for Mx, r2 = 0.93 for CCP, and r2 = 0.94 for nCPP. The 95% confidence intervals for the left-right differences were 20 cm/s for FVm, 0.16 for GPI, 0.18 for Mx, 13 mm Hg for CCP, and 4.6 mm Hg for nCPP. CONCLUSIONS: This study gives the reference values for the assessment of left-right symmetry of cerebral hemodynamics using various TCD-derived indices. These reference values should be useful for clinical studies assessing the left-right asymmetry of cerebral hemodynamics on a daily basis.

Dissociating speech perception and comprehension at reduced levels of awareness.

We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional inferior frontal and posterior temporal responses to ambiguous sentences provide a neural correlate of semantic processes critical for comprehending sentences containing ambiguous words. However, this additional response was absent during light sedation, suggesting a marked impairment of sentence comprehension. A significant decline in postscan recognition memory for sentences also suggests that sedation impaired encoding of sentences into memory, with left inferior frontal and temporal lobe responses during light sedation predicting subsequent recognition memory. These findings suggest a graded degradation of cognitive function in response to sedation such that "higher-level" semantic and mnemonic processes can be impaired at relatively low levels of sedation, whereas perceptual processing of speech remains resilient even during deep sedation. These results have important implications for understanding the relationship between speech comprehension and awareness in the healthy brain in patients receiving sedation and in patients with disorders of consciousness.

Hemodynamic steroid responsiveness is predictive of neurological outcome after traumatic brain injury.

INTRODUCTION: To determine the impact of physiologic doses of hydrocortisone on neurologic outcome after traumatic brain injury (TBI). METHODS: We conducted a retrospective study in a neurocritical care unit at a university teaching hospital. We included 29 patients with moderate and severe TBI requiring vasoactive drugs to maintain adequate arterial blood pressure who received corticosteroid. Infected patients were excluded. Blood cortisol levels were measured before and 30 and 60 minutes after the administration of a high-dose corticotropin stimulation test (HDST). Patients received hydrocortisone replacement therapy (200-300 mg/day) and vasoactive drugs requirements were noted. Intracranial pressure was managed according to a predefined protocol. RESULTS: A total of 14 out of 29 (48%) of patients were classified as responders to hydrocortisone (stopping vasoactive drugs within 3 days of starting hydrocortisone). The Glasgow Outcome Score (GOS) was used to assess neurologic outcome at 6 months. A favorable outcome (GOS 4 and 5) was observed in 11 out of 14 (79%) of responders and five out of 15 (33%) of nonresponders (p = 0.03). Of the responders, 12 out of 14 (85%) had a baseline cortisol below 414 nmol/L, and five out of 14 (36%) had primary adrenal insufficiency (AI) (primary AI: low baseline cortisol, and poor response to the HDST). Age, severity of injury, and response to hydrocortisone were predictive of outcome in multiple logistic regression analysis. CONCLUSIONS: Adrenal insufficiency is frequent after TBI, and hydrocortisone replacement therapy seems to be associated with a favorable neurologic outcome.