Does basiliximab induction trigger lifethreatening ARDS and shock in young patients after kidney transplantation?

BACKGROUND: Kidney disease Improving Global Outcomes (KDIGO) guidelines strongly recommend administering an anti-IL-2R mAb (i.e., basiliximab) for induction in all kidney transplant recipients. We describe a life-threatening episode of shock following basiliximab injection and review the literature. METHODS AND RESULTS: A 20-year-old male was given tacrolimus, methylprednisolone, mycophenolate, and basiliximab, 20 mg in the context of living-related kidney transplantation. On post-operative Day 1 (POD 1), he developed acute respiratory distress syndrome (ARDS), shock, multiple organ failure, and had a cardiac arrest. After effective resuscitation, he received rescue therapies (NO inhalation, extra-corporeal membrane oxygenation, and CVVHD) but lost the graft as the result of cortical necrosis. We conducted PubMed searches that yielded 7 similar cases; 6 required invasive ventilation. Three patients developed cardiac arrest, 3 required major inotropic support, and 2 developed MOF and myocardial depression. All but 1 patient recovered rapidly within a few days. There was no evidence for infectious, allergic, or over-hydration concerns. Although the direct causal role of basiliximab cannot be formally proven, the fact that ARDS at the time of induction therapy with other immunosuppressive agents is otherwise extremely rare suggests a direct role for basiliximab. CONCLUSIONS: Basiliximab could be associated with shock and ARDS.

Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often?

OBJECTIVES: To assess the use of antibiotic de-escalation in patients with hospital-acquired severe sepsis in an academic setting. DESIGN: We reviewed all episodes of severe sepsis treated over a 1-yr period in the department of intensive care. Antimicrobial therapy was considered as appropriate when the antimicrobial had in vitro activity against the causative microorganisms. According to the therapeutic strategy in the 5 days after the start of antimicrobial therapy, we classified patients into four groups: de-escalation (interruption of an antimicrobial agent or change of antibiotic to one with a narrower spectrum); no change in antibiotherapy; escalation (addition of a new antimicrobial agent or change in antibiotic to one with a broader spectrum); and mixed changes. SETTING: A 35-bed medico-surgical intensive care department in which antibiotic strategies are reviewed by infectious disease specialists three times per week. PATIENTS: One hundred sixty-nine patients with 216 episodes of severe sepsis attributable to a hospital-acquired infection who required broad-spectrum ß-lactam antibiotics alone or in association with other anti-infectious agents. MEASUREMENTS AND MAIN RESULTS: The major sources of infection were the lungs (44%) and abdomen (38%). Microbiological data were available in 167 of the 216 episodes (77%). Initial antimicrobial therapy was inappropriate in 27 episodes (16% of culture-positive episodes). De-escalation was applied in 93 episodes (43%), escalation was applied in 22 episodes (10%), mixed changes were applied in 24 (11%) episodes, and there was no change in empirical antibiotic therapy in 77 (36%) episodes. In these 77 episodes, the reasons given for maintaining the initial antimicrobial therapy included the sensitivity pattern of the causative organisms and previous antibiotic therapy. The number of episodes when the chance to de-escalate may have been missed was small (4 episodes [5%]). CONCLUSION: Even in a highly focused environment with close collaboration among intensivists and infectious disease specialists, de-escalation may actually be possible in <50% of cases.

Infection in the critically ill--questions we should be asking.

Best practice in infection control and management in the critically ill continues to generate considerable debate. The wide variation in current practice is witness to this continuing uncertainty. In large part this is due to the lack of a decent evidence base and to an over-reliance on deep-set dogma. Data that go against the grain are often conveniently overlooked and political imperatives frequently supervene. This article highlights some of these discrepancies and argues for a more balanced, scientific approach. In this time of financial restraint, we need to identify true priorities from both health and economic perspectives, and to see what practices can safely and effectively be modified or abandoned.

How can the response to volume expansion in patients with spontaneous respiratory movements be predicted?

INTRODUCTION: The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements. METHODS: The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask (n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure (PAOP), right atrial pressure (RAP), pulse pressure variation (DeltaPP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more. RESULTS: Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute-1 m-2 (medians and 25th and 75th centiles), p < 0.05. At baseline, DeltaPP varied between 0% and 49%. There were no significant differences in DeltaPP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area +/- SD: 0.73 +/- 0.13 for PAOP, p < 0.05 vs DeltaPP and 0.69 +/- 0.12 for RAP, p = 0.054 compared with DeltaPP) than with dynamic indices of preload (0.40 +/- 0.13 for DeltaPP and 0.53 +/- 0.13 for inspiratory changes in RAP, p not significant compared with DeltaPP). CONCLUSION: In patients with spontaneous respiratory movements, DeltaPP and inspiratory changes in RAP failed to predict the response to volume expansion.

Pulse pressure variations to predict fluid responsiveness: influence of tidal volume.

OBJECTIVE: To evaluate the influence of tidal volume on the capacity of pulse pressure variation (DeltaPP) to predict fluid responsiveness. DESIGN: Prospective interventional study. SETTING: A 31-bed university hospital medico-surgical ICU. PATIENTS AND PARTICIPANTS: Sixty mechanically ventilated critically ill patients requiring fluid challenge, separated according to their tidal volume. INTERVENTION: Fluid challenge with either 1,000 ml crystalloids or 500 ml colloids. MEASUREMENTS AND RESULTS: Complete hemodynamic measurements including DeltaPP were obtained before and after fluid challenge. Tidal volume was lower than 7 ml/kg in 26 patients, between 7-8 ml/kg in 9 patients, and greater than 8 ml/kg in 27 patients. ROC curve analysis was used to evaluate the predictive value of DeltaPP at different tidal volume thresholds, and 8 ml/kg best identified different behaviors. Overall, the cardiac index increased from 2.66 (2.00-3.47) to 3.04 (2.44-3.96) l/min m(2) ( P <0.001). It increased by more than 15% in 33 patients (fluid responders). Pulmonary artery occluded pressure was lower and DeltaPP higher in responders than in non-responders, but fluid responsiveness was better predicted with DeltaPP (ROC curve area 0.76+/-0.06) than with pulmonary artery occluded pressure (0.71+/-0.07) and right atrial (0.56+/-0.08) pressures. Despite similar response to fluid challenge in low (<8 ml/kg) and high tidal volume groups, the percent of correct classification of a 12% DeltaPP was 51% in the low tidal volume group and 88% in the high tidal volume group. CONCLUSIONS: DeltaPP is a reliable predictor of fluid responsiveness in mechanically ventilated patients only when tidal volume is at least 8 ml/kg.

Can changes in arterial pressure be used to detect changes in cardiac index during fluid challenge in patients with septic shock?

PURPOSE: Response to fluid challenge is often defined as an increase in cardiac index (CI) of more than 10-15%. However, in clinical practice CI values are often not available. We evaluated whether changes in mean arterial pressure (MAP) correlate with changes in CI after fluid challenge in patients with septic shock. METHODS: This was an observational study in which we reviewed prospectively collected data from 51 septic shock patients in whom complete hemodynamic measurements had been obtained before and after a fluid challenge with 1,000 ml crystalloid (Hartman's solution) or 500 ml colloid (hydroxyethyl starch 6%). CI was measured using thermodilution. Patients were divided into two groups (responders and non-responders) according to their change in CI (responders: %CI >10%) after the fluid challenge. Statistical analysis was performed using a two-way analysis of variance test followed by a Student's t test with adjustment for multiple comparisons. Pearson's correlation and receiver operating characteristic curve analysis were also used. RESULTS: Mean patient age was 67 ± 17 years and mean Sequential Organ Failure Assessment (SOFA) upon admittance to the intensive care unit was 10 ± 3. In the 25 responders, MAP increased from 69 ± 9 to 77 ± 9 mmHg, pulse pressure (PP) increased from 59 ± 15 to 67 ± 16, and CI increased from 2.8 ± 0.8 to 3.4 ± 0.9 L/min/m(2) (all p < 0.001). There were no significant correlations between the changes in MAP, PP, and CI. CONCLUSIONS: Changes in MAP do not reliably track changes in CI after fluid challenge in patients with septic shock and, consequently, should be interpreted carefully when evaluating the response to fluid challenge in such patients.