Feasibility, safety and efficacy of COVID-19 severe acute respiratory distress syndrome management without invasive mechanical ventilation.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible. METHODS: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS). RESULTS: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality. CONCLUSIONS: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Integration of pain scores, morphine consumption and demand/delivery ratio to evaluate patient-controlled analgesia: the C-SIA score.

BACKGROUND: Patient-controlled analgesia (PCA) is used to manage postoperative pain. Postoperatively, some patients need to be re-instructed on its correct use. This study explores the efficacy of re-instruction and illustrates a comprehensive version of the Silverman integrated approach (C-SIA), based on the integration of static and dynamic pain scores, morphine consumption, and the ratio between demanded and delivered PCA boluses (the DD ratio). METHODS: In total, 50 patients operated on for colorectal surgery were studied retrospectively. The change in DD ratio after re-instruction was analyzed as the primary endpoint. Re-instructed and not re-instructed subjects were compared according to DD ratio, pain scores, and morphine consumption. A secondary comparison was performed using the SIA and C-SIA scores, to illustrate the reliability of the latter tool. Agreement between C-SIA and SIA score was assessed using a Bland-Altman analysis. RESULTS: In re-instructed patients, the DD ratio decreased after re-education (P = 0.011). Re-instructed patients had higher DD ratios (P = 0.018) and pain scores at rest (P = 0.024) and movement (P = 0.012) at 24 h after surgery than not re-instructed subjects. These differences disappeared at the 48 h visit. Both the SIA and C-SIA scores reflected these findings. C-SIA scores showed a higher coefficient of correlation with the DD ratio (r = 0.815; P < 0.001) than SIA scores (r = 0.663; P < 0.001). The C-SIA scores, in absolute values, being based on more variables, were, on average, 2.5 times the SIA score. CONCLUSIONS: Re-instruction is effective for optimizing PCA therapy. The C-SIA is an alternative to the SIA score that gives an overall measure of PCA therapy efficacy.

Early postoperative cognitive dysfunction and postoperative delirium after anaesthesia with various hypnotics: study protocol for a randomised controlled trial--the PINOCCHIO trial.

BACKGROUND: Postoperative delirium can result in increased postoperative morbidity and mortality, major demand for postoperative care and higher hospital costs. Hypnotics serve to induce and maintain anaesthesia and to abolish patients' consciousness. Their persisting clinical action can delay postoperative cognitive recovery and favour postoperative delirium. Some evidence suggests that these unwanted effects vary according to each hypnotic's specific pharmacodynamic and pharmacokinetic characteristics and its interaction with the individual patient.We designed this study to evaluate postoperative delirium rate after general anaesthesia with various hypnotics in patients undergoing surgical procedures other than cardiac or brain surgery. We also aimed to test whether delayed postoperative cognitive recovery increases the risk of postoperative delirium. METHODS/DESIGN: After local ethics committee approval, enrolled patients will be randomly assigned to one of three treatment groups. In all patients anaesthesia will be induced with propofol and fentanyl, and maintained with the anaesthetics desflurane, or sevoflurane, or propofol and the analgesic opioid fentanyl.The onset of postoperative delirium will be monitored with the Nursing Delirium Scale every three hours up to 72 hours post anaesthesia. Cognitive function will be evaluated with two cognitive test batteries (the Short Memory Orientation Memory Concentration Test and the Rancho Los Amigos Scale) preoperatively, at baseline, and postoperatively at 20, 40 and 60 min after extubation.Statistical analysis will investigate differences in the hypnotics used to maintain anaesthesia and the odds ratios for postoperative delirium, the relation of early postoperative cognitive recovery and postoperative delirium rate. A subgroup analysis will be used to categorize patients according to demographic variables relevant to the risk of postoperative delirium (age, sex, body weight) and to the preoperative score index for delirium. DISCUSSION: The results of this comparative anaesthesiological trial should whether each the three hypnotics tested is related to a significantly different postoperative delirium rate. This information could ultimately allow us to select the most appropriate hypnotic to maintain anaesthesia for specific subgroups of patients and especially for those at high risk of postoperative delirium. REGISTERED AT TRIAL.GOV NUMBER: ClinicalTrials.gov: NCT00507195.

Postoperative cognitive dysfunction: toward the Alzheimer's disease pathomechanism hypothesis.

Alzheimer's disease (AD), a chronic and progressive deterioration of memory and other cognitive domains, is the most common form of dementia. Because of related health and social impact, there is growing interest in assessing potential relationship between anesthesia and the onset and progression of chronic neurodegenerative disorders, including AD. Currently, preclinical and clinical research is addressed to identify underlying pathomechanisms, patient risk factors, and the use of the least provocative drugs and techniques, to minimize the incidence of chronic neurodegenerative disorders. Preclinical studies are providing an increasing body of evidences on some of the mechanisms that link anesthetics to neuronal programmed cell death (apoptosis) and accumulation of misfolded proteins in the aging brain. Therefore, risk factors and pathomechanisms of chronic neurodegenerative disorders, including AD, and persistent postoperative-postanesthesia cognitive dysfunction may overlap.

Early postoperative cognitive recovery and gas exchange patterns after balanced anesthesia with sevoflurane or desflurane in overweight and obese patients undergoing craniotomy: a prospective randomized trial.

Overweight and obese patients are at especially high risk for delayed awakening after general surgery. Whether this risk also applies to cerebral neurosurgical procedures remains unclear. This study evaluated early postoperative cognitive recovery and gas exchange patterns, after balanced anesthesia with sevoflurane or desflurane, in overweight and obese patients undergoing craniotomy for supratentorial expanding lesions. Fifty-six patients were consecutively enrolled, and randomly assigned to 1 of 2 study groups to receive balanced anesthesia with sevoflurane or desflurane. Cognitive function was evaluated with the Short Orientation Memory Concentration Test and the Rancho Los Amigos Scale and gas exchange patterns (pH, PaO2, and PaCO2) were recorded in all patients at 5 time-points: preoperatively and postoperatively, after patients reached an Aldrete score >or=9, at 15, 30, 45, and 60 minutes. Preoperative cognitive status was similar in the 2 treatment groups. Early postoperative cognitive recovery was more delayed and Short Orientation Memory Concentration Test scores at 15 and 30 minutes postanesthesia were lower in patients receiving sevoflurane-based anesthesia than in those receiving desflurane-based anesthesia (21.5+/-3.5 vs. 14.9+/-3.5) (P<0.005) and (26.9+/-0.7 vs. 21.5+/-1.4) (P<0.005), and the postoperative Rancho Los Amigos Scalegrade 8 showed a similar trend (25/28 patients 89% vs. 8/28 patients 28% (P<0.005) and 28/28 patients (100% vs. 13/28 patients 46%) (P<0.005). Similarly, gas-exchange analysis showed higher PaCO2 at 15 and 30 minutes and lower pH up to 45 minutes postextubation in patients receiving sevoflurane-based anesthesia. In overweight and obese patients undergoing craniotomy desflurane-based anesthesia allows earlier postoperative cognitive recovery and reversal to normocapnia and normal pH.

Esmolol blunts postoperative hemodynamic changes after propofol-remifentanil total intravenous fast-track neuroanesthesia for intracranial surgery.

STUDY OBJECTIVE: To investigate whether esmolol is effective in attenuating postoperative hemodynamic changes related to sympathetic overdrive. DESIGN: Clinical study. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA physical status I, II, and III patients, age 18 to 65 years, scheduled for elective craniotomy for supratentorial neurosurgery. INTERVENTIONS: Patients were given total intravenous anesthesia (TIVA) during emergence from anesthesia and up to 60 minutes after extubation. Those patients who had hypertension (defined as an increase in systolic blood pressure >20% from baseline values) and tachycardia (defined as an increase >20% in heart rate from baseline) received a loading dose of 500 microg/kg esmolol in one minute, followed by an infusion titrated stepwise (50, 100, 200, and 300 microg/kg per min) every two minutes. MEASUREMENTS: The mean dose and duration of esmolol therapy were measured. MAIN RESULTS: Of 60 patients, 49 (82%) who received propofol-remifentanil TIVA developed significant tachycardia and hypertension soon after extubation. Treatment with esmolol (500 microg/kg in bolus maintained at a mean rate of 200 +/- 50 microg/kg per min) effectively controlled hypertension and tachycardia in 45 of 49 patients (92%; P < 0.05) within a mean 4.30 +/- 2.20 minutes. After extubation, mean esmolol infusion time was 29 +/- 8 minutes. CONCLUSION: In patients undergoing elective neurosurgery with propofol-remifentanil TIVA, a relatively small esmolol dose and short infusion time effectively blunts early postoperative arterial hypertension and tachycardia.

Intensive insulin therapy after severe traumatic brain injury: a randomized clinical trial.

INTRODUCTION: To investigate the risks and possible benefits of routine versus intensive insulin therapy, assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl (<4.44 mmol/l) in patients admitted to the intensive care unit (ICU) after severe traumatic brain injury (TBI). METHODS AND RESULTS: Ninety-seven patients admitted after severe TBI, were enrolled and randomly assigned to two groups of target glycemia. Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl (12.22 mmol/l) or at intensive rates, to maintain glycemia at 80-120 mg/dl (4.44-6.66 mmol/l). The following primary and outcome variables were measured during follow-up: hypoglycemic episodes, duration of ICU stay, infection rate, and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale (GOS). Episodes of hypoglycemia (defined as blood glucose <80 mg/dl or 4.44 mmol/l) were significantly higher in patients receiving intensive insulin therapy: median (min-max) conventional insulin therapy 7 (range 0-11) vs. intensive insulin therapy 15 (range 6-33); P<0.0001. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs. 10.0 days; P < 0.05); while infection rates during ICU stay (25.0% vs. 38.8%, P = 0.15), and GOS scores and mortality at 6 months were similar in the two groups. CONCLUSIONS: Intensive insulin therapy significantly increases the risk of hypoglycemic episodes. Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy, both groups have similar follow-up mortality and neurologic outcome. Hence if intensive insulin therapy is to be used, great effort must be taken to avoid hypoglycemia.

Endotracheal lidocaine in preventing endotracheal suctioning-induced changes in cerebral hemodynamics in patients with severe head trauma.

INTRODUCTION: In patients with severe head trauma, endotracheal suctioning can result in adverse reactions including cough, systemic hypertension, increased intracranial pressure, and reduced cerebral perfusion pressure. The aim of this prospective, blinded clinical trial in mechanically ventilated patients with severe head trauma whose cough reflexes were still intact was to assess the effectiveness of endotracheally instilled lidocaine in preventing endotracheal suctioning-induced changes in cerebral hemodynamics (increase in intracranial pressure and reduced cerebral perfusion pressure) after a single endotracheal suctioning. METHODS AND RESULTS: Ten minutes after lidocaine instillation into the endotracheal tube, secretions were suctioned for <30 s through a standard closed endotracheal suctioning circuit. Heart rate, arterial pressure, intracranial pressure, and cerebral perfusion pressure were continuously monitored. The first patient studied received an endotracheal lidocaine dose of 2.0 mg/kg. The dose for the next study patient was titrated upwards or downwards in 0.5 mg/kg steps according to, whether the intracranial pressure reached the predefined threshold of > or =20 mmHg. A total of 41 patients were studied. Lidocaine instillation into the endotracheal tube had no effect on hemodynamic and ventilatory variables. In 21 patients lidocaine dose instilled into the endotracheal tube effectively prevented the endotracheal suctioning-induced intracranial pressure increase behind the predefined threshold of > or =20 mmHg and cerebral perfusion pressure remained unchanged. In the remaining 20, although intracranial pressure rose significantly cerebral perfusion pressure remained constant. CONCLUSIONS: In mechanically ventilated patients with severe head trauma endotracheal lidocaine instillation effectively and dose-dependently prevents the endotracheal suctioning-induced intracranial pressure increase and cerebral perfusion pressure reduction.

The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome, and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective pilot trial.

It is unclear if avoiding hyperglycemia during intensive care after acute brain injury improves morbidity, mortality, and neurologic outcome. This prospective randomized trial tested whether intensive insulin therapy affected infection rates, vasospasm, mortality, or long-term neurologic outcome in subarachnoid hemorrhage patients during their intensive care unit (ICU) stay. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcome measure was infection rate until the fourteenth postoperative day in the ICU or until patient discharge. Secondary end points were the incidence of vasospasm until the fourteenth postoperative day in the ICU or until patient discharge, and neurologic outcome and mortality at 6 months follow-up. A total of 78 patients were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy (38 and 40 patients, respectively). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than in patients who received intensive insulin therapy (42% vs. 27%; P<0.001). The incidence of vasospasm during the study was also similar in conventional and intensive therapy groups (31.5% vs. 27.6% in the conventional and intensive insulin therapy groups; P=0.9). Overall mortality rates at 6 months were similar in the 2 groups (18% vs.15%; P=0.9), as was the neurologic outcome at 6 months [modified Rankin score >3 in 22/38 patients (57.8%) in the conventional therapy group vs. 21/40 patients (52.5%) in the intensive insulin therapy group; P=0.7]. Intensive insulin therapy in patients with acute subarachnoid hemorrhage admitted to a postoperative neurosurgical ICU after surgical clipping of intracranial aneurysms decreases infection rates. The benefit of strict glycemic control on postoperative vasospasm, neurologic outcome, and mortality rates does not seem to be affected by intensive insulin therapy.