High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood-brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.

Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium.

BACKGROUND: Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr). METHODS: Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality. RESULTS: Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients. CONCLUSIONS: Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915).

Management of tight intraoperative glycemic control during off-pump coronary artery bypass surgery in diabetic and nondiabetic patients.

OBJECTIVES: To optimize intra- and postoperative insulin management in cardiac surgical patients. DESIGN: A prospective, randomized, open-label, single-center study. SETTING: A large nonuniversity hospital. PARTICIPANTS: Sixty diabetics and 60 nondiabetics undergoing off-pump cardiac bypass surgery. INTERVENTIONS: Intra- and postoperative tight glycemic control were achieved using different approaches with a modified insulin protocol. MEASUREMENTS AND MAIN RESULTS: Nondiabetics were divided randomly: in the ND-ind group (n = 30), insulin was started at induction according to preinduction blood glucose (BG) concentrations. In group ND >110 (n = 30), insulin was started when BG concentrations exceeded 110 mg/dL during surgery. Up to 85% of the ND >110 group started on insulin intraoperatively. Intraoperatively, the ND-ind group had more BG within target (80-110 mg/dL) (p = 0.002), less BG >130 mg/dL (p = 0.015), and more BG between 70 and 79 mg/dL (p = 0.002). In diabetics, BG concentration was checked every 30 (DM-30), n = 30) versus 60 minutes (DM-60, n = 30) to improve the protocol's performance. Intraoperatively, there were more BG concentrations within target (80-110 mg/dL) (p = 0.02) and less >130 mg/dL (p = 0.0002) in the DM-30 group. During surgery, the hyperglycemic index and the glycemic penalty index were lower in the ND-ind group (p < 0.05). Postoperatively, the mean BG concentrations, hyperglycemic index, and glycemic penalty index in diabetics and nondiabetics were comparable between groups (p < 0.05). In the overall 2,641 BG samples, the lowest BG concentration in the operating room was 71 and in the intensive care unit (ICU) it was 61 mg/dL. CONCLUSIONS: In diabetics and nondiabetics undergoing off-pump coronary artery bypass surgery, tight perioperative glycemic control is feasible and efficient, with minimal risks for hypo- and hyperglycemia. In nondiabetics, starting insulin therapy from induction onwards results in more measurements within target, without affecting the mean BG. In diabetics, decreasing the sampling interval from 60 to 30 minutes results in more measurements within target and in a mean blood glucose within target at ICU arrival.

Development and performance of a two-step desflurane-O(2)/N(2)O fresh gas flow sequence.

STUDY OBJECTIVE: To determine if the previously described single-step O(2)/N(2)O fresh gas flow (FGF) sequence could be combined with a simple desflurane vaporizer (F(D)) sequence to maintain the end-expired desflurane (F(A)des) at 4.5% with the anesthesia delivery unit machine (ADU Anesthesia Machine(R); General Electric, Helsinki, Finland). DESIGN: Prospective randomized clinical study. SETTING: Onze Lieve Vrouw Hospital, Aalst, Belgium, a large teaching hospital. PATIENTS: 42 ASA physical status I and II patients requiring general endotracheal anesthesia and controlled mechanical ventilation. INTERVENTIONS: In 18 patients undergoing general anesthesia with controlled mechanical ventilation, F(D) was determined to maintain F(A)des at 4.5% with O(2)/N(2)O FGF of two and 4 L per minute for three minutes and 0.3 and 0.4 L per minute thereafter. Using the same FGF sequence, we prospectively tested the F(D) schedule that approached this observed F(D) pattern with the fewest possible adjustments in another 24 patients. MAIN RESULTS: F(D) of 6.5% for 15 minutes followed by 5.5% thereafter approximated the observed F(D) course well. When it was prospectively tested, the median (25th, 75th percentiles) performance error was -1% (-5.1%, 5.2%); absolute performance error, 7.1% (3.9%, 9.5%); divergence, -6.6% per hour (23.1%, 3.1%/h); and wobble, 2.2% (1.8%, 3.2%). Because F(A)des increased above 4.9%, F(D) was decreased in 5 patients after 23 minutes (0.5% decrement once or twice); in two patients, F(D) was temporarily increased. In one patient, FGF was temporarily increased because the bellows volume became insufficient. CONCLUSIONS: One O(2)/N(2)O rotameter FGF setting change from 6 to 0.7 L per minute after three minutes and one desflurane F(D) change from 6.5% to 5.5% after 15 minutes maintained anesthetic gas concentrations within predictable and clinically acceptable limits during the first 20 minutes.

Desflurane Consumption During Automated Closed-circuit Delivery is Higher Than When a Conventional Anesthesia Machine is Used With a Simple Vaporizer-O2-N2O Fresh Gas Flow Sequence.

BACKGROUND: The Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N2. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O2-N2O administration schedule that allows early FGF reduction. METHODS: Thirty-four ASA PS I or II patients undergoing plastic, urologic, or gynecologic surgery received desflurane in O2/N2O. In the ADU group (n = 24), an initial 3 min high FGF of O2 and N2O (2 and 4 L.min-1, respectively) was used, followed by 0.3 L.min-1 O2 + 0.4 L.min-1 N2O. The desflurane vaporizer setting (FD) was 6.5% for the first 15 min, and 5.5% during the next 25 min. In the Zeus group (n = 10), the Zeus® was used in automated closed circuit anesthesia mode with a selected end-expired (FA) desflurane target of 4.6%, and O2/N2O as the carrier gases with a target inspired O2% of 30%. Desflurane FA and consumption during the first 40 min were compared using repeated measures one-way ANOVA. RESULTS: Age and weight did not differ between the groups (P > 0.05), but patients in the Zeus group were taller (P = 0.04). In the Zeus group, the desflurane FA was lower during the first 3 min (P < 0.05), identical at 4 min (P > 0.05), and slightly higher after 4 min (P < 0.05). Desflurane consumption was higher in the Zeus group at all times, a difference that persisted after correcting for the small difference in FA between the two groups. CONCLUSION: Agent consumption with an automated closed-circuit anesthesia machine is higher than with a conventional anesthesia machine when the latter is used with a specific vaporizer-FGF sequence. Agent consumption during automated delivery might be further reduced by optimizing the algorithm(s) that manages the initial FGF or by tolerating some N2 in the circuit to minimize the need for intermittent flushing.