Efficacy and safety of ceftobiprole in patients aged 65 years or older:a post hoc analysis of three Phase III studies

Lay abstract Infections are a common cause of severe disease and death in older patients. Antibiotic treatment may also be complicated by age-related changes within the body. The present study analyzed results from three large clinical trials that assessed the benefits of the novel antibiotic ceftobiprole in the older population. In patients aged over 65 years with skin infections or with pneumonia acquired either in the community or in a hospital setting, ceftobiprole offered similar benefits to established antibiotics. There was also some preliminary evidence that older patients may respond more quickly to ceftobiprole compared with the other antibiotics used in these studies. Overall, ceftobiprole was well tolerated and will be a useful treatment option for infections in older patients. Aim: To evaluate the efficacy and safety of ceftobiprole in patients aged >= 65 years. Materials & methods: We conducted a post hoc analysis of three randomized, double-blind, Phase III studies in patients with acute bacterial skin and skin structure infections, community-acquired pneumonia and hospital-acquired pneumonia. Results: Findings for patients aged >= 65 years (n = 633) were consistent with those for the overall study populations, although a trend toward improved outcomes was reported in some subgroups, for example, patients aged >= 75 years with community-acquired pneumonia were more likely to achieve an early clinical response with ceftobiprole than comparator (treatment difference 16.3% [95% CI:1.8-30.8]). The safety profile was similar between treatment groups in all studies. Conclusion: This analysis further supports the efficacy and safety of ceftobiprole in older patients with acute bacterial skin and skin structure infections or pneumonia. Clinicaltrials.gov trial identifiers: , ,

Noninvasive pulse pressure variation and stroke volume variation to predict fluid responsiveness at multiple thresholds : a prospective observational study

Pulse pressure variation (PPV) and stroke volume variation (SVV) are dynamic preload variables that can be measured noninvasively to assess fluid responsiveness (FR) in anesthetized patients with mechanical ventilation. Few studies have examined the effectiveness of predicting FR according to the definition of FR, and assessment of inconclusive values of PPV and SVV around the cut-off value (the "grey zone") might improve individual FR prediction. We explored the ability of noninvasive volume clamp derived measurements of PPV and SVV to predict FR using the grey zone approach, and we assessed the influence of multiple thresholds on the predictive ability of the numerical definition of FR. Ninety patients undergoing general surgery were included in this prospective observational study and received a 500 mL fluid bolus as deemed clinically required by the attending anesthesiologist. A minimal relative increase in stroke volume index (a dagger SVI) was used to define FR with different thresholds from 10-25%. The PPV, SVV, and SVI were measured using the NexfinA (R) device that employs noninvasive volume clamp plethysmography. The area under the receiver operator characteristic curve gradually increased for PPV / SVV with higher threshold values (from 0.818 / 0.760 at 10% a dagger SVI to 0.928 / 0.944 at 25% a dagger SVI). The grey zone limits of both PPV and SVV changed from 9-16% (PPV) and 5-13% (SVV) at the 10% a dagger SVI threshold to 18-21% (PPV) and 14-16% (SVV) at the 25% a dagger SVI threshold. Noninvasive PPV and SVV measurements allow an acceptable FR prediction, although the reliability of both variables is dependent on the intended increase in SVI, which improves substantially with concomitant smaller grey zones at higher a dagger SVI thresholds

Hemodynamics and tissue oxygenation during balanced anesthesia with a high antinociceptive contribution:an observational study

BACKGROUND: In particular surgical conditions, a balanced anesthesia with a high-antinociceptive contribution is required. This may induce cardiovascular impairment and thus compromise tissue oxygenation. In this prospective observational study, we investigated the hemodynamic stability and tissue oxygen saturation (StO2) in 40 patients with a high-antinociceptive general anesthesia, goal-directed fluid therapy, and norepinephrine. In addition, optimal surgical conditions and safe and fast emergence are pivotal parts of anesthetic management. METHODS: In high-antinociceptive propofol/remifentanil anesthesia with bispectral index (BIS) between 40 and 60, norepinephrine was administered to maintain mean arterial pressure (MAP) above 80% of individual baseline. Fluid was administered if the ∆ plethysmographic waveform amplitude exceeded 10%. Surgical and recovery conditions, hemodynamic responses, and tissue oxygenation were investigated. RESULTS: Mean (SD) StO2 at the left thenar eminence increased from 83 (6)% before to 86 (4)% 20 min after induction of anesthesia (p <0.05). Cardiac index dropped from 3.0 (0.7) to 2.1 (0.4) L min(-1) (p <0.05), MAP from 109 (16) to 83 (14) mm Hg, and heart rate from 73 (12) to 54 (8) bpm (p <0.05). Thirteen out of 40 patients received a fluid bolus. The median (range) norepinephrine administration rate was 0.05 (0.0-0.10) μg kg(-1) min(-1). After complete akinesia in all patients during surgery, a median (IQR) extubation time of 311 (253-386) s was observed. CONCLUSIONS: This high-antinociceptive balanced anesthesia with goal-directed fluid and vasopressor therapy adequately preserved StO2 and hemodynamic homeostasis. TRIAL REGISTRATION: ISRCTN20153044

Additional postoperative cell salvage of shed mediastinal blood in cardiac surgery does not reduce allogeneic blood transfusions: a cohort study

OBJECTIVES: Does additional postoperative collection and processing of mediastinal shed blood with a cell salvage device reduce the number of allogeneic blood transfusions compared to intraoperative cell salvage alone? METHODS: A single-centre cohort study in which adult patients with coronary artery bypass grafting or aortic valve replacement were allocated to either a C.A.T.S(®) group with intraoperative blood processing only or a CardioPat(®) group with both intra- and postoperative blood processing. The primary endpoint was the number of allogeneic blood transfusions during hospital admission. RESULTS: The study included 99 patients; 50 in the C.A.T.S(®) and 49 in the CardioPat(®) group.There was no difference in the number of red blood cells (RBC) (C.A.T.S(®) group 43 units versus CardioPat(®) 50 units, p=0.74), fresh frozen plasma (C.A.T.S(®) 8 units versus CardioPat(®) 8 units, p=1.00) or platelets (C.A.T.S(®) 5 units versus CardioPat(®) 4 units, p=1.00) transfused during the hospital stay.Cardiac creatinine kinase (CK-MB) and troponin levels did not differ between the groups although a significant time effect (p<0.001) was present. Creatinine kinase (CK) levels were not different between the groups three hours after arrival in the intensive care unit (ICU) (CardioPat(®) group versus C.A.T.S(®) group, p=0.17). But, compared to the C.A.T.S(®) group on the first (350 [232-469] IU/L) and second postoperative days (325 [201-480] IU/L), the increase in CK levels was more in the CardioPat(®) group on the first (431 [286-642] IU/L, p=0.02) and second postoperative days (406 [239-760] IU/L, p=0.05), resulting in a difference between the groups (p=0.04) CONCLUSIONS: Postoperative cell salvage does not reduce transfusion requirements compared to intraoperative cell salvage alone, but results in elevated total CK levels that suggest haemolysis

Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia: a randomised controlled trial

BACKGROUND: Phenylephrine and norepinephrine are two vasopressors commonly used to counteract anaesthesia-induced hypotension. Their dissimilar working mechanisms may differentially affect the macro and microcirculation, and ultimately tissue oxygenation. OBJECTIVES: We investigated the differential effect of phenylephrine and norepinephrine on the heart rate (HR), stroke volume (SV), cardiac index (CI), cerebral tissue oxygenation (SctO(2)) and peripheral tissue oxygenation (SptO(2)), and rate-pressure product (RPP). DESIGN: A randomised controlled study. SETTING: Single-centre, University Medical Center Groningen, The Netherlands. PATIENTS: Sixty normovolaemic patients under balanced propofol/remifentanil anaesthesia. INTERVENTIONS: If the mean arterial pressure (MAP) dropped below 80% of the awake state value, phenylephrine (100 mu g + 0.5 mu g kg(-1) min(-1)) or norepinephrine (10 mu g + 0.05 mu g kg(-1) min(-1)) was administered in a randomised fashion. MAIN OUTCOME MEASURES: MAP, HR, SV, CI, SctO(2), SptO(2) and rate-pressure product (RPP) analysed from 30 s before drug administration until 240 s thereafter. RESULTS: Phenylephrine and norepinephrine caused an equivalent increase in MAP [Delta = 13 (8 to 22) and Delta = 13 (9 to 19) mmHg, respectively] and SV [Delta = 6 +/- 6 and Delta = 5 +/- 7 ml, respectively], combined with a significant equivalent decrease in HR (both Delta = -8 +/- 6 bpm), CI (both Delta = -0.2 +/- 0.3 l min(-1) m(-2)) and SctO(2) and an unchanged RPP (Delta = 345 +/- 876 and Delta = 537 +/- 1076 mmHg min(-1)). However, SptO(2) was slightly but statistically significantly (P < 0.05) decreased after norepinephrine [Delta = -3 (-6 to 0)%] but not after phenylephrine administration [Delta = 0 (-1 to 1)%]. In both groups, SptO(2) after vasopressor was still higher than the awake value. CONCLUSION: In normovolaemic patients under balanced propofol/remifentanil anaesthesia, phenylephrine and norepinephrine produced similar clinical effects when used to counteract anaesthesia-induced hypotension. After norepinephrine, a fall in peripheral tissue oxygenation was statistically significant, but its magnitude was not clinically relevant

Oxygen reserve index : validation of a new variable

BACKGROUND: Pulse oximetry-derived oxygen saturation is typically >97% in normoxia and hyperoxia, limiting its clinical use. The new Oxygen Reserve Index (ORi), a relative indicator of the partial pressure of oxygen dissolved in arterial blood (Pao(2)) in the range of 100-200 mm Hg, may allow additional monitoring of oxygen status. METHODS: In this prospective validation intervention study, 20 healthy volunteers were breathing standardized oxygen concentrations ranging from mild hypoxia (fraction of inspired oxygen = 0.14) to hyperoxia (fraction of inspired oxygen = 1.0) via a tight-fitting face mask. ORi was measured noninvasively by multiwavelength pulse co-oximetry using 2 finger sensors. These ORi values (unitless scale, 0.00-1.00) were compared with measured Pao(2) values. Repeated-measurements correlation analysis was performed to assess the ORi/Pao(2) relationship. ORi trending ability was assessed using a 4-quadrant plot. The area under the receiver operating characteristics curve was calculated to assess the prediction of hypoxia (low-ranged Pao(2), <100 mm Hg). RESULTS: Within the ORi-sensitive range, a strong positive correlation was found between ORi and Pao(2) for both sensors (R = 0.78 and 0.83; P < .0001). ORi trending of Pao(2) was good within this range (concordance rate = 94%). The prediction of Pao(2) <100 mm Hg was also good, with an area under the receiver operating characteristics curve of 0.91 and 99% sensitivity and 82% specificity. CONCLUSIONS: In this prospective volunteer validation study, a strong and positive correlation between Pao(2) and ORi was found, together with a good trending ability. Based on these data, the future use of ORi as a continuous noninvasive monitoring tool for assessing oxygenation status in patients receiving supplemental oxygen might be supported