Background
Anaphylaxis is recognized mainly through clinical criteria, which may lack specificity or relevance in the perioperative setting. The transient increase in serum tryptase has been proposed ...since 1989 as a diagnostic tool. Sampling for well‐defined acute and baseline determinations has been recommended. We assessed the performance of four proposed algorithms with tightly controlled time frames for tryptase sampling, their robustness with inadequate sampling times, and the possible use of mature tryptase determination.
Methods
A retrospective study was performed on 102 adult patients from the Aix‐Marseille University Hospitals who had experienced a perioperative hypersensitivity reaction clinically suggesting anaphylaxis. EAACI and ICON criteria were used to diagnose anaphylaxis. Mature and total serum tryptase levels were measured.
Results
Based on EAACI guidelines, clinical diagnostic criteria for anaphylaxis were found in 76 patients and lacking in 26. The most effective algorithm was the international consensus recommendation of 2012 that acute total tryptase levels should be greater than (1.2×baseline tryptase + 2 μg/L to be considered a clinically significant rise. In our cohort, this algorithm achieved 94% positive predictive value (PPV), 53% negative predictive value (NPV), 75% sensitivity, 86% specificity, and a Youden's index value of 0.61. A detectable acute mature tryptase level showed lower sensitivity, particularly in patients with acute total tryptase levels lower than 16 μg/L. Acute tryptase levels varied as a function of the clinical severity of anaphylaxis.
Conclusion
Total tryptase levels in serum discriminated between nonanaphylactic and anaphylactic events in a perioperative setting when acute and baseline levels were collected and analyzed by the consensus algorithm.
The 2012 consensus that acute tryptase should be greater than (1.2 × baseline tryptase) + 2 μg/L performs best among four algorithms for tryptase interpretation during perioperative anaphylaxis. The 2012 consensus that acute tryptase should be greater than (1.2 × baseline tryptase) + 2 μg/L performs best for reaction grades 2, 3 and 4. Higher anaphylaxis grades are associated with higher levels of acute tryptase and more prevalent if baseline tryptase levels are above 5 μg/L.PPV: Positive predictive value; NPV: Negative predictive value
To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients.
Prospective ...randomized study.
ICU.
Liver transplant recipients over a period of 1 year (N=40).
The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared.
Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued.
The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group.
The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.
OBJECTIVETo assess the effect on outcome (1 yr) of decompressive craniectomy performed within or after the first 24 hrs posttrauma in severely head-injured trauma patients with intractable cerebral ...hypertension.
DESIGNRetrospective cohort study.
SETTINGSIntensive care unit of a university hospital.
PATIENTSAmong 816 patients with severe head trauma (Glasgow Coma Scale ≤8), 40 underwent decompressive craniectomy. After data collection, patients were divided into two groupsearly and late decompressive craniectomy. An early decompressive craniectomy was performed within the first 24 hrs in patients according to the following criteriaa Glasgow Coma Scale score <6 and the existence of clinical signs of cerebral herniation (absence of pupillary reflexes), correlated with abnormalities in computed tomography scan including hematoma, appearance of diffuse or unilateral brain swelling, and/or cerebral herniation. The intracranial pressure in these patients was not measured before the decompressive craniectomy was performed. A late decompressive craniectomy (>24 hrs) was performed according to following criteriaan intractable intracranial hypertension with intracranial pressure >35 mm Hg, a unilateral or bilateral absence of pupillary reflexes, and the same abnormalities in computed tomography scan as previously described.
INTERVENTIONTwenty-seven patients with signs of cerebral herniation required the procedure at the time of initial evacuation of a mass lesion. In 13 patients, decompressive craniectomy was performed because of elevated intracranial pressure refractory to medical treatment consisting of cerebrospinal fluid derivation, deep sedation, osmotherapy, hyperventilation, and nesdonal or propofol.
MEASUREMENTS AND MAIN RESULTSFive patients (19%) in whom an early decompressive craniectomy was performed had good recoveries (social rehabilitation), eight patients (30%) remained in a persistent vegetative state or with a severe disability, and 14 died (52%). On the other hand, the performance of late decompressive craniectomy in case of medical treatment failure was followed by social rehabilitation in five patients (38%) and death in three patients (23%). A persistent vegetative state or a severe disability was observed in five patients (38%). Meningitis or cerebral abscess occurred in six patients after decompressive craniectomy and were easily cured by antibiotic treatment.
CONCLUSIONSIn 40 patients with intractable intracranial hypertension and at very high risk of brain death, decompressive craniectomy allowed 25% of patients to attain social rehabilitation at 1 yr.
Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to ...plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance. Using plasma sample spiked with LMVs featuring different levels of PGC, we demonstrated that CD15-beads specifically extracted LMVs. The MV dependency of the test was demonstrated using electron microscopy, high speed centrifugation, nanofiltration and detergent-mediated solubilization and the MV-PGC specificity using plasmin-specific inhibitors, or antibodies blocking elastase or uPA. Thanks to a reaction booster (ε-ACA), we showed that the assay was more sensitive and reproducible than the original method. Moreover, it exhibited a good repeatability, inter-operator and inter-experiment reproducibility. The new immunomagnetic bio-assay was further validated in patients with septic shock. As a result, we showed that MV-PGC values were significantly lower in septic shock patients who died compared to patients who survived, both at inclusion and 24 h later (1.4 0.8-3.0 vs 3.1 1.7-18 A
405
× 10
−3
/min, p = 0.02; 1.4 1-1.6 vs 5.2 2.2-16 A
405
× 10
−3
/min, p = 0.004). Interestingly, combining both MV-PGC and PAI-1 in a ratio significantly improved the predictive value of PAI-1. This strategy, a hybrid capture bioassay to specifically measure LMV-PGC using for the first time, opens new perspectives for measuring subcellular fibrinolytic potential in clinical settings with fibrinolytic imbalance.
Hyperoxia is common during liver transplantation (LT), without being supported by any guidelines. Recent studies have shown the potential deleterious effect of hyperoxia in similar models of ...ischemia-reperfusion. Hyperoxia after graft reperfusion during orthotopic LT could increase lactate levels and worsen patient outcomes.
We conducted a retrospective and monocentric pilot study. All adult patients who underwent LT from 26 July 2013 to 26 December 2017 were considered for inclusion. Patients were classified into two groups according to oxygen levels before graft reperfusion: the hyperoxic group (PaO
> 200 mmHg) and the nonhyperoxic group (PaO
< 200 mmHg). The primary endpoint was arterial lactatemia 15 min after graft revascularization. Secondary endpoints included postoperative clinical outcomes and laboratory data.
A total of 222 liver transplant recipients were included. Arterial lactatemia after graft revascularization was significantly higher in the hyperoxic group (6.03 ± 4 mmol/L) than in the nonhyperoxic group (4.81 ± 2 mmol/L),
< 0.01. The postoperative hepatic cytolysis peak, duration of mechanical ventilation and duration of ileus were significantly increased in the hyperoxic group.
In the hyperoxic group, the arterial lactatemia, the hepatic cytolysis peak, the mechanical ventilation and the postoperative ileus were higher than in the nonhyperoxic group, suggesting that hyperoxia worsens short-term outcomes and could lead to increase ischemia-reperfusion injury after liver transplantation. A multicenter prospective study should be performed to confirm these results.
Background
In patients with severe sepsis, no randomized clinical trial has tested the concept of de-escalation of empirical antimicrobial therapy. This study aimed to compare the de-escalation ...strategy with the continuation of an appropriate empirical treatment in those patients.
Methods
This was a multicenter non-blinded randomized noninferiority trial of patients with severe sepsis who were randomly assigned to de-escalation or continuation of empirical antimicrobial treatment. Recruitment began in February 2012 and ended in April 2013 in nine intensive care units (ICUs) in France. Patients with severe sepsis were assigned to de-escalation (
n
= 59) or continuation of empirical antimicrobial treatment (
n
= 57). The primary outcome was to measure the duration of ICU stay. We defined a noninferiority margin of 2 days. If the lower boundary of the 95 % confidence interval (CI) for the difference in patients assigned to the de-escalation group was less than 2 days, as compared with that of patients assigned to the continuation group, de-escalation was considered to be noninferior to the continuation strategy. Secondary outcomes included mortality at 90 days, occurrence of organ failure, number of superinfections, and number of days with antibiotics during the ICU stay.
Results
The median duration of ICU stay was 9 interquartile range (IQR) 5–22 days in the de-escalation group and 8 IQR 4–15 days in the continuation group, respectively (
P
= 0.71). The mean difference was 3.4 (95 % CI −1.7 to 8.5). A superinfection occurred in 16 (27 %) patients in the de-escalation group and six (11 %) patients in the continuation group (
P
= 0.03). The numbers of antibiotic days were 9 7–15 and 7.5 6–13 in the de-escalation group and continuation group, respectively (
P
= 0.03). Mortality was similar in both groups.
Conclusion
As compared to the continuation of the empirical antimicrobial treatment, a strategy based on de-escalation of antibiotics resulted in prolonged duration of ICU stay. However, it did not affect the mortality rate.
OBJECTIVE:To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function.
DESIGN:Prospective, randomized, open-label ...study.
SETTING:Intensive care unit of a university, tertiary, and referral center.
PATIENTS:Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation.
INTERVENTIONS:Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured.
MEASUREMENTS AND MAIN RESULTS:Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 ± 17 to 104 ± 11 beats·min, p < .01) and cardiac index (from 5.1 ± 1.7 to 4.2 ± 1.6 L·min·m) was observed, with no change in stroke volume. Oxygen delivery index (from 784 ± 131 to 701 ± 92 mL·min·m) and consumption index (from 244 ± 69 to 210 ± 54 mL·min·m) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs.
CONCLUSIONS:In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.
OBJECTIVE:To assess the rate of appropriateness of empirical antimicrobial therapy for ventilator-associated pneumonia, to evaluate de-escalation in patients with ventilator-associated pneumonia ...treated according to local pathway, and to identify the bacteria responsible for recurrence of ventilator-associated pneumonia.
DESIGN:Prospective observational study during a 36-month period.
SETTING:Medical-surgical intensive care unit of a university hospital.
PATIENTS:One hundred and fifteen patients hospitalized in an intensive care unit developing ventilator-associated pneumonia with positive cultures. The patients with ventilator-associated pneumonia were treated with limited-spectrum antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had no prior hospitalization (within 21 days) or prior administration of antibiotics (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal aspiration were used to reassess empirical therapy.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:A limited-spectrum therapy was used in 79 patients (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The mortality rate was significantly higher in the patients in whom empirical therapy was inappropriate than in those in whom treatment was appropriate (47 vs. 20%, p = .04). De-escalation was done in respectively 26% and 72% of patients with early- and late-onset ventilator-associated pneumonia, whereas treatment was escalated in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in 22 cases, including eight episodes due to high-risk bacteria.
CONCLUSIONS:A rational empirical antimicrobial therapy for ventilator-associated pneumonia using limited-spectrum antibiotics is possible if local ecology and patient medical history and clinical status are considered. In addition, de-escalation is feasible in 42% of patients. This integrative approach may reduce the emergence of resistant bacteria, which in turns reduces the need for broad-spectrum antibiotics, breaking the vicious circle of antibiotic overuse.
IMPORTANCE: Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. OBJECTIVE: To evaluate ...whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. DESIGN, SETTING, AND PARTICIPANTS: The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). INTERVENTIONS: Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient’s resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. RESULTS: Among 298 patients who were randomized, 292 patients completed the trial (mean SD age, 70 7 years; 44 15.1% women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, −14%, 95% CI, −25% to −2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality. CONCLUSIONS AND RELEVANCE: Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01536470
OBJECTIVE:To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock.
DESIGN:Prospective, open-label, randomized, controlled study.
...SETTING:Medical-surgical intensive care unit of a tertiary care teaching hospital.
PATIENTS:Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure ≥60 mm Hg.
INTERVENTIONS:Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groupsIn the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine.
MEASUREMENTS AND MAIN RESULTS:Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8–6.0) to 5.8 (4.3–6.9) L·min·m. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variablesurine flow, 63 (14–127) and 70 (15–121) mL; serum creatinine, 170 (117–333) and 153 (112–310) μmol·L; and creatinine clearance, 50 (12–77) and 67 (13–89) mL·min·1.73 m.
CONCLUSIONS:Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function.
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