Aims
Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by ...continuous administration of prophylactic cefuroxime compared to bolus administration.
Methods
Twelve patients undergoing elective cardiac surgery were investigated. Group A received 1.5 g cefuroxime as bolus infusions before surgery, and 12 and 24 hours thereafter. In group B, a continuous infusion of 3.0 g cefuroxime was started after a bolus of 1.5 g. Cefuroxim levels were determined in blood and tissue (microdialysis). T‐test, Wilcoxon signed rank test and χ2 test were used for statistical analysis.
Results
The area under the curve (AUC) of plasma cefuroxime concentrations was greater in group B (399 333–518) as compared to group A (257 177–297 h mg L−1, median and interquartile range, P = .026). Furthermore, a significantly longer percentage of time > minimal inhibitory concentrations of 2 mg L−1 (100% vs 50%), 4 mg L−1 (100% vs 42%), 8 mg L−1 (100% vs 17%) and 16 mg L−1 (83% vs 8%) was found for free plasma cefuroxime in group B. In group B, area under the curve in subcutaneous tissue (78 61–113 h mg L−1) and median peak concentration (33 26–38 mg L−1) were markedly higher compared to group A (P = 0.041 and P = .026, respectively).
Conclusions
Higher cefuroxime concentrations were measured in plasma and subcutaneously over a prolonged period of time when cefuroxime was administered continuously. The clinical implication of this finding still has to be elucidated.
Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury ...by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions.
We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS.
After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62-0.79) in the left lung vs 0.14 (IQR 0.14-0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (C
) of the left lung occurred immediately, whereas C
of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs.
We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.
Monitoring for thrombosis and hemolysis is crucial for patients under extracorporeal or mechanical circulatory support, but it can be costly. We investigated correlations between hemolysis index (HI) ...and plasma-free hemoglobin (PFH) levels on one hand, and between the HI and plasma lactate dehydrogenase (LDH) levels on the other, in critically ill patients with and without extracorporeal or mechanical circulatory support. Additionally, we calculated the cost reductions if monitoring through HI were to replace monitoring through PFH or plasma LDH. In a single-center study, HI was compared with PFH and plasma LDH levels in blood samples taken for routine purposes in critically ill patients with and without extracorporeal or mechanical circulatory support. A cost analysis, restricted to direct costs associated with each measurement, was made for an average 10-bed ICU. This study included 147 patients: 56 patients with extracorporeal or mechanical circulatory support (450 measurements) and 91 patients without extracorporeal or mechanical circulatory support (562 measurements). The HI correlated well with PFH levels (r = 0.96;
< 0.01) and poorly with plasma LDH levels (r = 0.07;
< 0.01) in patients with extracorporeal or mechanical circulatory support. Similarly, HI correlated well with PFH levels (r = 0.97;
< 0.01) and poorly with plasma LDH levels (r = -0.04;
= 0.39) in patients without extracorporeal or mechanical circulatory support. ROC analyses demonstrated a strong performance of HI, with the curve indicating excellent discrimination in the whole cohort (area under the ROC of 0.969) as well as in patients under ECMO or mechanical circulatory support (area under the ROC of 0.988). Although the negative predictive value of HI for predicting PFH levels > 10 mg/dL was high, its positive predictive value was found to be poor at various cutoffs. A simple cost analysis showed substantial cost reduction if HI were to replace PFH or plasma LDH for hemolysis monitoring. In conclusion, in this cohort of critically ill patients with and without extracorporeal or mechanical circulatory support, HI correlated well with PFH levels, but poorly with plasma LDH levels. Given the high correlation and substantial cost reductions, a strategy utilizing HI may be preferable for monitoring for hemolysis compared to monitoring strategies based on PFH or plasma LDH. The PPV of HI, however, is unacceptably low to be used as a diagnostic test.
We investigated driving pressure (ΔP) and mechanical power (MP) and associations with clinical outcomes in critically ill patients ventilated for reasons other than ARDS.
Individual patient data ...analysis of a pooled database that included patients from four observational studies of ventilation. ΔP and MP were compared among invasively ventilated non–ARDS patients with sepsis, with pneumonia, and not having sepsis or pneumonia. The primary endpoint was ΔP; secondary endpoints included MP, ICU mortality and length of stay, and duration of ventilation.
This analysis included 372 (11%) sepsis patients, 944 (28%) pneumonia patients, and 2040 (61%) patients ventilated for any other reason. On day 1, median ΔP was higher in sepsis (14 11-18 cmH2O) and pneumonia patients (14 11-18cmH2O), as compared to patients not having sepsis or pneumonia (13 10-16 cmH2O) (P < 0.001). Median MP was also higher in sepsis and pneumonia patients. ΔP, as opposed to MP, was associated with ICU mortality in sepsis and pneumonia patients.
The intensity of ventilation differed between patients with sepsis or pneumonia and patients receiving ventilation for any other reason; ΔP was associated with higher mortality in sepsis and pneumonia patients.
This post hoc analysis was not registered; the individual studies that were merged into the used database were registered at clinicaltrials.gov: NCT01268410 (ERICC), NCT02010073 (LUNG SAFE), NCT01868321 (PRoVENT), and NCT03188770 (PRoVENT–iMiC).
•Ventilation intensity differs between various categories of non–ARDS patients•ΔP is higher in sepsis and in pneumonia patients than in those receiving ventilation for any other reason•ΔP is associated with ICU mortality in sepsis and pneumonia patients
After major surgery, longitudinal changes in resting energy expenditure (REE) as well as imbalances in oxygen delivery (DO2) and distribution and processing (VO2) may occur due to dynamic metabolic ...requirements, an impaired macro- and microcirculatory flow and mitochondrial dysfunction. However, the longitudinal pattern of these parameters in critically ill patients who die during hospitalization remains unknown. Therefore, we analyzed in 566 patients who received a pulmonary artery catheter (PAC) their REE, DO2, VO2 and oxygen extraction ratio (O2ER) continuously in survivors and non-survivors over the first 7 days post cardiac surgery, calculated the percent increase in the measured compared with the calculated REE and investigated the impact of a reduced REE on 30-day, 1-year and 6-year mortality in a uni- and multivariate model. Only in survivors was there a statistically significant transition from a negative to a positive energy balance from day 0 until day 1 (Day 0: −3% (−18, 14) to day 1: 5% (−9, 21); p < 0.001). Furthermore, non-survivors had significantly decreased DO2 during the first 4 days and reduced O2ER from day 2 until day 6. Additionally, a lower REE was significantly associated with a worse survival at 30 days, 1 year and 6 years (p = 0.009, p < 0.0001 and p = 0.012, respectively). Non-survivors seemed to be unable to metabolically adapt from the early (previously called the ‘ebb’) phase to the later ‘flow’ phase. DO2 reduction was more pronounced during the first three days whereas O2ER was markedly lower during the following four days, suggesting a switch from a predominantly limited oxygen supply to prolonged mitochondrial dysfunction. The association between a reduced REE and mortality further emphasizes the importance of REE monitoring.
Reduced oxygen consumption (VO
), either due to insufficient oxygen delivery (DO
), microcirculatory hypoperfusion and/or mitochondrial dysfunction, has an impact on the adverse short- and long-term ...survival of patients after cardiac surgery. However, it is still unclear whether VO
remains an efficient predictive marker in a population in which cardiac output (CO) and consequently DO
is determined by a left ventricular assist device (LVAD). We enrolled 93 consecutive patients who received an LVAD with a pulmonary artery catheter in place to monitor CO and venous oxygen saturation. VO
and DO
of in-hospital survivors and non-survivors were calculated over the first 4 days. Furthermore, we plotted receiver-operating curves (ROC) and performed a cox-regression analysis. VO
predicted in-hospital, 1- and 6-year survival with the highest area under the curve of 0.77 (95%CI: 0.6-0.9;
= 0.0004). A cut-off value of 210 mL/min VO
stratified patients regarding mortality with a sensitivity of 70% and a specificity of 81%. Reduced VO
was an independent predictor for in-hospital, 1- and 6-year mortality with a hazard ratio of 5.1 (
= 0.006), 3.2 (
= 0.003) and 1.9 (
= 0.0021). In non-survivors, VO
was significantly lower within the first 3 days (
= 0.010,
< 0.001,
< 0.001 and
= 0.015); DO
was reduced on days 2 and 3 (
= 0.007 and
= 0.003). In LVAD patients, impaired VO
impacts short- and long-term outcomes. Perioperative and intensive care medicine must, therefore, shift their focus from solely guaranteeing sufficient oxygen supply to restoring microcirculatory perfusion and mitochondrial functioning.
Abstract Background One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ...ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. Methods “POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)” is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. Discussion POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. Trial registration Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.
The investigation of biomarkers associated with undesired outcome following lung transplantation (LuTX) is essential for a better understanding of the underlying pathophysiology, an earlier ...identification of susceptible recipients and the development of targeted therapeutic options. We therefore determined the longitudinal perioperative course of putative cytokines related to neutrophil activation (chemokine CC motif ligand 4 (CCL-4), interleukin (IL)-23 and Lipocalin 2 (LCN2)) and a cytokine that has been implicated in graft-versus-host disease (Follistatin-like 1 (FSTL1)) in 42 consecutive patients undergoing LuTX. We plotted receiver-operating curves (ROC) to assess the predictive power of the measured cytokines for short-term outcomes namely primary graft dysfunction (PGD), early complications requiring extracorporeal membrane oxygenation (ECMO), and a high postoperative sequential organ failure assessment (SOFA). All cytokines increased immediately after surgery. ROC analyses determined significant associations between CCL4 and a high SOFA score (area under the curve (AUC) 0.74 (95%CI:0.5−0.9; p < 0.05), between LCN2 and postoperative ECMO support (AUC 0.73 (95%CI:0.5−0.9; p < 0.05), and between FSTL1 and PGD (AUC 0.70 (95%CI:0.5−0.9; p < 0.05). The serum concentrations of the neutrophil-derived cytokines LCN2 and CCL4 as well as FSTL1 were all related to poor outcome after LuTX. The specific predictive power, however, still has to be assessed in larger trials. The potential role of FSTL1 as a biomarker in the development of PGD could be of great interest particularly since this protein appears to play a crucial role in allograft tolerance.
Neurological complications after heart surgery are associated with tremendous morbidity and mortality. Nonconvulsive status epilepticus (NCSE), which can only be verified by EEG, may cause secondary ...brain damage. Its frequency and its impact on outcomes after cardiac surgery is still unclear. We collected the neurological files and clinical data of all our patients after heart surgery who, in the course of their ICU stay, had been seen by a neurologist who ordered an EEG. Within 18 months, 1457 patients had cardiac surgery on cardiopulmonary bypass. EEG was requested for 89 patients. Seizures were detected in 39 patients and NCSE was detected in 11 patients. Open heart surgery was performed in all 11 NSCE patients, of whom eight showed concomitant brain insults. None had a history of epilepsy. Despite the inhibition of seizure activity with antiseizure medication, clinical improvement was only noted in seven NCSE patients, three of whom were in cerebral performance category 2 and four in category 3 at hospital discharge. The four patients without neurological benefit subsequently died in the ICU. The occurrence of NCSE after open cardiac surgery is significant and frequently associated with brain injury. It seems prudent to perform EEG studies early to interrupt seizure activity and mitigate secondary cerebral injury.
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