Pharmacodynamic analysis of a fluid challenge with 4 ml kg-1 over 10 or 20 min: a multicenter cross-over randomized clinical trial.

PURPOSE: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg-1. METHODS: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg-1 of crystalloids in 10 (FC10) or 20 (FC20) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), time when the dmax was observed (tmax), change from baseline at 1-min (d1) and 5-min (d5) after FC end. RESULTS: After FC10 and FC20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The dmax and the tmax were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end. CONCLUSIONS: The infusion time of FC administration affects fluid responsiveness, being higher for FC10 as compared to FC20. The effect on flow variables of either FCs fades 5 min after the end of infusion.

Electrophysiological and olfactometric evaluation of long-term COVID-19.

COVID-19 is a public health emergency with cases increasing globally. Its clinical manifestations range from asymptomatic and acute respiratory disease to multiple organ dysfunction syndromes and effects of COVID-19 in the long term. Interestingly, regardless of variant, all COVID-19 share impairment of the sense of smell and taste. We would like to report, as far as we know, the first comprehensive neurophysiological evaluation of the long-term effects of SARS-CoV-2 on the olfactory system with potential-related neurological damage. The case report concerns a military doctor, with a monitored health history, infected in April 2020 by the first wave of the epidemic expansion while on military duty in Codogno (Milan). In this subject, we find the electrophysiological signal in the periphery, while its correlate is absent in the olfactory bulb region than in whole brain recordings. In agreement with this result is the lack of metabolic signs of brain activation under olfactory stimulation. Consequently, quantitative and qualitative diagnoses of anosmia were made by means of olfactometric tests. We strongly suggest a comprehensive series of olfactometric tests from the first sign of COVID-19 and subsequent patient assessments. In conclusion, electrophysiological and metabolic tests of olfactory function have made it possible to study the long-term effects and the establishment of neurological consequences.

Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial.

BACKGROUND: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. METHODS: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6-8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. RESULTS: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. CONCLUSIONS: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. TRIAL REGISTRATION: registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

Assessment of Fluid Responsiveness in Prone Neurosurgical Patients Undergoing Protective Ventilation: Role of Dynamic Indices, Tidal Volume Challenge, and End-Expiratory Occlusion Test.

BACKGROUND: In patients in the prone position, the reliability of pulse pressure variation and stroke volume variation (PPV and SVV) and the use of functional hemodynamic tests to predict fluid responsiveness have not previously been established. Perioperatively, in this setting, optimizing fluid management can be challenging, and fluid overload is associated with both intraoperative and postoperative complications. We designed this study to assess the sensitivity and specificity of baseline PPV and SVV, the tidal volume (VT) challenge (VTC) and the end-expiratory occlusion test (EEOT) in predicting fluid responsiveness during elective spinal surgery. METHODS: The study protocol was started during a period of intraoperative hemodynamic stability after prone positioning and before the administration of any vasopressor: (1) at baseline, the controlled ventilation was set at 6 mL/kg of predicted body weight (PBW) (T0); (2) patients underwent the first EEOT (EEOT6) by interrupting the mechanical ventilation for 30 seconds; (3) the ventilation was set again at 6 mL/kg PBW for 1 minute (T1); (4) the VTC was applied by increasing the VT up to 8 mL/kg PBW for 1 minute; (5) the ventilation was kept at 8 mL/kg PBW for 1 minute (T2); (6) a second EEOT (EEOT8) was performed; (7) the VT was reduced back to 6 mL/kg PBW for 1 minute (T3); (8) a fluid challenge of 250 mL of Ringer's solution was infused over 10 minutes. After each step, a complete set of hemodynamic measurements was recorded. RESULTS: Neither PPV and SVV values recorded at T3 nor the EEOT6 or the EEOT8 predicted fluid responsiveness. The change in PPV after VTC application predicted fluid responsiveness with an area under the curve of 0.96 (95% confidence interval, 0.87-1.00), showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 12.2%. The change in SVV after VTC application predicted fluid responsiveness with an area under the curve 0.96 (95% confidence interval, 0.89-1.00) showing a sensitivity of 95.2% and a specificity of 94.7%, using a cutoff increase of 8.0%. A linear correlation between stroke volume index changes after fluid challenge administration and the changes in PPV and SVV after VTC application was observed (r = 0.71; P < .0001 and r = 0.68; P < .0001, respectively). CONCLUSIONS: In prone elective neurosurgical patients, the baseline values of PPV and SVV and the EEOT fail to predict fluid responsiveness, while the VTC is a very reliable functional hemodynamic test and could be helpful in guiding intraoperative fluid therapy.

Tidal volume challenge to predict fluid responsiveness in the operating room: An observational study.

BACKGROUND: Pulse pressure variation (PPV) and stroke volume variation (SVV) do not predict fluid responsiveness when using a protective ventilation strategy: the use of functional haemodynamic tests can be useful to overcome this limitation. OBJECTIVES: We tested the use of a tidal volume challenge (VTC), during 6 ml kg [predicted body weight (PBW)] ventilation, and the end-expiratory occlusion test (EEOT) for prediction of fluid responsiveness. DESIGN: An interventional prospective study. SETTING: Supine elective neurosurgical patients. INTERVENTIONS: The study protocol was, first, the initial EEOT test was performed during baseline 6 ml kg PBW ventilation; second, VTC was performed by increasing the VT up to 8 ml kg PBW and PPV and SVV changes were recorded after 1 min; third, a second EEOT was performed during 8 ml kg PBW ventilation; and VT was reduced back to 6 ml kg PBW and a third EEOT was performed. Finally, a 250 ml fluid challenge was administered over 10 min to identify fluid responders (increase in stroke volume index ≥10%). RESULTS: In the 40 patients analysed, PPV and SVV values at baseline and EEOT performed at 6 ml kg PBW did not predict fluid responsiveness. A 13.3% increase in PPV after VTC predicted fluid responsiveness with a sensitivity of 94.7% and a specificity of 76.1%, while a 12.1% increase in SVV after VTC predicted fluid responsiveness with a sensitivity of 78.9% and a specificity of 95.2%. After EEOT performed at 8 ml kg PBW, a 3.6% increase in cardiac index predicted fluid responsiveness with a sensitivity of 89.4% and a specificity of 85.7%, while a 4.7% increase in stroke volume index (SVI) with a sensitivity of 89.4% and a specificity of 85.7%. CONCLUSION: The changes in PPV and SVV obtained after VTC are reliable and comparable to the changes in CI and SVI obtained after EEOT performed at 8 ml kg PBW in predicting fluid responsiveness in neurosurgical patients. TRIAL REGISTRATION: ACTRN12618000351213.

Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial.

PURPOSE: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure. METHODS: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality. RESULTS: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies. CONCLUSIONS: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Anesthesiology Resident Induction Month: a pilot study showing an effective and safe way to train novice residents through simulation.

BACKGROUND: The transition of new residents from medical school to the post-graduate clinical environment remains challenging. We hypothesized that an introductory simulation course could improve new residents' performance in anesthesiology. METHODS: The Anesthesiology Residents Induction Month (ARIM) program was designed as a non-clinical simulation training program aiming at providing the theoretical and practical skills to safely approach, as junior anesthesiologists, the operating rooms. For each participant, specific knowledge, procedural skills and non-technical performance were assessed with a pre and post-test approach, before and immediately after the participation in the study. RESULTS: Fifteen first-month residents participated in the study. As compared to pre-test, residents significantly improved in all three evaluated areas. Pre-test knowledge assessment mean improved from 56% to 73% in the post-test (P<0.001). In the procedural skills assessment, pre-test mean improved from 43% to 77% (P<0.001) and non-technical skills assessment improved from 3.17 to 4.61 (in a scale out of seven points) in the post-test (P<0.001). CONCLUSIONS: Data suggest that an intensive simulation-based program can be an effective way for first-year residents to rapidly acquire and develop basic skills specific to anesthesiology. There might be benefits to begin residency with a training program aiming at developing and standardizing technical and non-technical skills.

Changes in respiratory and hemodynamic parameters during low-dose propofol sedation in combination with regional anesthesia for herniorrhaphy and genitourinary surgery in children.

BACKGROUND: Spontaneous vs mechanical ventilation during propofol sedation has been a subject of debate. We evaluated the safety of low-dose propofol sedation as an adjunct to regional anesthesia during herniorrhaphy and genitourinary surgery in infants and children. METHODS: The study was conducted in a prospective, nonrandomized manner using a consecutive sample of 62 American Society of Anesthesiologists physical status class I patients between 5 months to 11 years of age in the surgery unit of an urban University Hospital. Propofol sedation (4-8 mg x kg(-1) x h(-1) continuous infusion) was used with regional anesthesia (caudal, ilioinguinal/iliohypogastric nerve or penile block with 0.2-0.375% ropivacaine). All children were spontaneously breathing without an anesthesia circuit. Respiratory and hemodynamic parameters were continuously recorded on all patients. One-way analysis of variance (ANOVA) for repeated measurements was used to analyze changes in respiratory and hemodynamic parameters during the procedure. RESULTS: Spontaneous ventilation was maintained in all patients with minimal changes in hemodynamic parameters. Heart rate, mean arterial pressure, and P(E)CO(2) remained stable throughout the study period: 23/62 (37%) patients exhibited signs of developing intrinsic endexpiratory pressure (PEEPi) or the presence of PEEPi because of progressive reduction of expiratory time. CONCLUSIONS: Low-dose propofol sedation in combination with regional anesthesia for elective herniorrhaphy and genitourinary surgery in children maintains spontaneous ventilation and has minimal effects on hemodynamic parameters for sedation lasting <1 h. The presence of PEEPi is a relative contraindication to the use of this regimen in children with asthma or history of upper airway infections.