Changes of the nociceptive flexion reflex threshold in patients undergoing cardiac surgery-a prospective clinical pilot study.

Opioid dosage for general anaesthesia and sedation relies on surrogate parameters such as heartrate and blood pressure. This implies the risk of both under- and overdosing. A promising tool to provide target-oriented opioid dosing is measuring the nociceptive flexion reflex threshold (NFRT). The aim of this study was to investigate the individual trajectories and to determine this methods' clinical practicability in the perioperative setting of cardiac surgery. NFRT was measured preoperatively (twice as baseline), immediately after surgery and later in the general ward (primary outcomes). No intraoperative measurements were performed since neuromuscular blockade hinders NFRT assessment. Administered analgesics and pain scores were also recorded (secondary outcomes). Data were collected from August 2019 to March 2020. 264 patients scheduled for cardiac surgery were screened for eligibility. 55 patients were included, 30 rendered datasets for analysis. Thresholds after conclusion of surgery [TICU: median (IQR), 31.1 mA (21.5-50.0 mA)] were significantly higher than preoperatively [Tpre: 9.2 mA (5.4-13.4 mA); P < 0.001]. In 11 patients (36.7%), no immediate postoperative reflex response was elicited. Later, all reflexes returned, but thresholds remained significantly higher than preoperatively [Tpost: 11.9 mA (9.2-16.6 mA); P = 0.043]. NFRT values after surgery were higher compared to baseline measurements. Subsequently they decreased but did not reach their baseline levels. There was no corresponding dose-dependency, suggesting multimodal effects on the nociceptive system. Unless measurements are not prevented by technical issues NFRT-assessment appears to be a future tool to target analgesics in patients not able to self-report pain. Trial registration Study registration: DRKS00021617. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021617 (registered retrospectively).

Validity of hospital ICD-10-GM codes to identify anaphylaxis.

PURPOSE: Anaphylaxis (ANA) is an important adverse drug reaction. We examined positive predictive values (PPV) and other test characteristics of ICD-10-GM code algorithms for detecting ANA as used in a multinational safety study (PASS). METHODS: We performed a cross-sectional study on routine data from a German academic hospital (2004-2019, age ≥ 18). Chart review was used for case verification. Potential cases were identified from the hospital administration system. The main outcome required at least one of the following: any type of specific in-hospital code (T78.2, T88.6, and T80.5) OR specific outpatient code in combination with a symptom code OR in-hospital non-specific code (T78.4, T88.7, and Y57.9) in combination with two symptom codes. PPV were calculated with 95% confidence interval. Sensitivity analyses modified type of codes, unit of analysis, verification criteria and time period. The most specific algorithm used only primary codes for ANA (numbers added in brackets). RESULTS: Four hundred and sixteen eligible cases were evaluated, and 78 (37) potential ANA cases were identified. PPV were 62.8% (95% CI 51.1-73.5) (main) and 77.4% (58.9-90.4) (most specific). PPV from all modifications ranged from 12.9% to 80.6%. The sensitivity of the main algorithm was 66.2%, specificity 91.5%, and negative predictive value 92.6%. Corresponding figures for the most specific algorithm were 32.4%, 98.0%, and 87.0%. CONCLUSIONS: The PPV of the main algorithm seems of acceptable validity for use in comparative safety research but will underestimate absolute risks by about a third. Restriction to primary discharge codes markedly improves PPV to the expense of reducing sensitivity.

The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial.

BACKGROUND: This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis. METHODS: This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity. RESULTS: 1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0-45.9) and 43.1 (10.1-184.0)). CONCLUSIONS: MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux.

BACKGROUND: Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. METHODS: Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety-Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. RESULTS: Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from -0.38 (2.18) to -2.41(2.43) µmol min 100 g. CONCLUSIONS: Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study.

INTRODUCTION: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. METHODS: In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. RESULTS: Median time to AT was 2.1 (IQR 0.8 - 6.0) hours and 3 hours (-0.1 - 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). CONCLUSIONS: A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.

[Case report - hemodynamic variables of a deep hypothermic patient over the period of external rewarming]. / Kasuistik - Hämodynamik während nicht invasiver Wiedererwärmung bei schwerer akzidenteller Hypothermie.

Deep accidental hypothermia is a very rare emergency, most of these patients die despite of immediate and adaequate therapy. We report on a hypothermic patient who was in a stable hemodynamic condition and breathing spontaneously at a temperature of 25.5°C. He was rewarmed with non-invasive methods. We describe and discuss the hemodynamic variables of an advanced monitoring during the time of external rewarming.

A randomized open label, parallel-group study to evaluate the hemodynamic effects of Cafedrine/Theodrenaline vs Noradrenaline in the treatment of intraoperative hypotension after induction of general anesthesia: the "HERO" study design and rationale.

OBJECTIVE: Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. RESEARCH DESIGN AND METHODS: This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III-IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection ("bolus phase", 0-20 min after initial application) and subsequently as continuous infusion ("infusion phase", 21-40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. RESULTS: Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the "infusion phase" and the treatment-related difference in average cardiac index during the "bolus phase" are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. CONCLUSION: This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the "HERO"-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.

Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial.

CONTEXT: Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. OBJECTIVE: To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. DESIGN, SETTING, AND PATIENTS: A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. INTERVENTIONS: Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. MAIN OUTCOME MEASURE: Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. RESULTS: Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). CONCLUSION: Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00534287.

[Effects of advanced haemodynamic monitoring on perioperative outcome in high-risk patients]. / Hämodynamisches Monitoring - Verbessertes Outcome durch erweitertes perioperatives hämodynamisches Monitoring.

Advanced haemodynamic monitoring provides information on blood flow, volume status, and oxygen supply to demand ratio. Together with related therapeutic algorithms these variables can be used to optimize cardiac preload and oxygen delivery in the perioperative period. There is increasing evidence that a goal-directed therapy can improve perioperative outcome. In this review we will briefly describe different target variables and their relevance for the haemodynamic optimization of high-risk surgical patients.

[Disorientation and delirium assessment : A secondary analysis of a prospective, observational study]. / Bedeutung der Desorientierung bei der Delireinschätzung : Sekundäranalyse einer prospektiven, observationellen Studie.

Disorientation may present as a warning sign of developing delirium. The most commonly used delirium assessment tool in Germany, the Confusion Assessment Method for Intensive Care Unit (CAM-ICU), does not rate "disorientation", since intubated patients cannot communicate verbally. However, the majority of German ICU patients are not orally intubated, so they could be examined for their orientation. This study was carried out to investigate whether the delirium feature "disorientation" in extubated patients yields diverging findings in comparison to the CAM-ICU and whether the sensitivity of the CAM-ICU may be improved when combined with the feature "disorientation" (CAM-IMC). A total of 86 paired assessments were completed in 50 extubated patients. Delirium was found in 19.8% (N = 17). The CAM-ICU had a sensitivity of 71% (95% confidence interval [CI] 44-90%) and a specificity of 100% (95-100%). Disorientation, if taken as the only delirium feature, had a sensitivity of 77% (50-93%) and a specificity of 93% (89-100%). The CAM-IMC reached a sensitivity of 88% (64-99%) and a specificity of 100% (95-100%). The receiver operating characteristics (ROC) analyses found an area under the curve (AUC) of 0.941 (95%CI 0.851-1.000) for the CAM-IMC, which was the highest compared to the other delirium tests (CAM-ICU, AUC 0.853 [0.720-0.986]; disorientation, AUC 0.868 [0.745-0.991]). This research emphasizes the importance of the feature "disorientation" for delirium assessments in patients able to verbally communicate and explains some controversial delirium ratings in daily practice. The CAM-IMC appears to be an attractive tool for delirium assessment in nonintubated patients and deserves further research.

(1 → 3)-ß-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial.

PURPOSE: To investigate whether (1 → 3)-ß-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI). METHODS: Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality. RESULTS: 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80-1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0-2.2] days in the BDG group and 4.4 (IQR 2.0-9.1, p < 0.01) days in the control group. CONCLUSIONS: Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock-A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study).

Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES: This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock. DESIGN: Multicenter, randomized, and placebo-controlled study. SETTING AND PARTICIPANTS: Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction. MAIN OUTCOMES AND MEASURES: Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives. RESULTS: Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups. CONCLUSIONS AND RELEVANCE: Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.

Effective Cerebral Perfusion Pressure: Does the Estimation Method Make a Difference?

INTRODUCTION: The effective cerebral perfusion pressure (CPPe), zero-flow pressure (ZFP), and resistance area product (RAP) are important determinants of cerebral blood flow. ZFP and RAP are usually estimated by linear regression analysis of pressure-velocity relationships of the middle cerebral artery. The aim of this study was to validate 4 other estimation methods against the standard linear regression method. METHODS: In a previous study, electroencephalography, arterial blood pressure, and middle cerebral artery flow velocity were measured in patients during internal cardioverter defibrillator implantation procedures to determine the electroencephalography frequency ranges that represent ischemic changes during periods of circulatory arrest. In this secondary analysis, arterial blood pressure and middle cerebral artery flow velocity were used to estimate CPPe, ZFP, and RAP by 4 different methods-the 3-point intercept calculation (LR3, systolic/mean/diastolic) and methods described by Czosnyka (systolic/diastolic), Belford (mean/diastolic), and Schmidt (systolic/diastolic)-and compare them with the reference linear regression method. CPPe was calculated as the difference between mean arterial pressure and ZFP. The primary endpoint was the difference, correlation, and agreement of these differently estimated CPPe measurements. RESULTS: In total, 174 measurements in 35 patients were collected under steady-state conditions before the first circulatory arrest phase during internal cardioverter defibrillator testing. CPPe, ZFP, and RAP measurements based on the 3-point intercept and Czosnyka calculation methods showed small mean differences, good agreement, low percentage errors, and excellent correlation when compared with the reference method. Agreement and correlation were moderate for the Belford method and unsatisfactory for the Schmidt method. CONCLUSIONS: CPPe, ZFP, and RAP measurements based on 2 alternative calculation methods are comparable to the linear regression reference method.

Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro.

PURPOSE: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects. METHODS: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H2O2) or vincristine. RESULTS: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H2O2 or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (α-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids. CONCLUSION: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids.

Continuous monitoring of ScvO(2) by a new fibre-optic technology compared with blood gas oximetry in critically ill patients: a multicentre study.

OBJECTIVE: The aim of this study was to compare the accuracy of the CeVOX monitor measuring continuous central venous saturation (ScvO(2)) with laboratory blood gas oximetry under clinical circumstances. DESIGN: Prospective, multicentre, observational study. SETTING: Five adult general intensive care units. PATIENTS AND PARTICIPANTS: Fifty-three critically ill patients. INTERVENTIONS: The fibre-optic probe was inserted into an ordinary central venous catheter's distal lumen. Blood samples were taken from this line via a Y-adapter every 8 h and ScvO(2) was measured with a laboratory co-oximeter. Patients were observed for a maximum of 5 days. Results were compared using linear regression and the Bland and Altman plots. MEASUREMENTS AND RESULTS: The 526 matched pairs of ScvO(2) showed a significant correlation between the two methods (r = 0.79, p< 0.001). Bland-Altman plots showed an overall mean bias of -0.3% and moderate agreement (lower and upper levels of agreement: -13.2% and 12.5%). Correlation for the first time point, and for differences between the first two time points for each method revealed good correlation: (n = 53): r = 0.79, p< 0.001; (n = 50): r = 0.58, p< 0.001, respectively. CONCLUSION: These results in a heterogeneous group of critically ill patients show that continuous ScvO(2) monitoring by the CeVOX technology yielded results comparable with those obtained by laboratory co-oximetry and therefore can be relied on in everyday clinical practice.