Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial.

STUDY OBJECTIVE: To assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial. DESIGN: Randomized controlled pilot trial. SETTING: Perioperative care in a tertiary care teaching hospital with outpatient follow-up. PATIENTS: One hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls. INTERVENTIONS: Randomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists. MEASUREMENTS: An experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes. MAIN RESULTS: The Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ±â€¯25% vs. 49 ±â€¯28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%). CONCLUSIONS: Intraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery. A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD. TRIAL REGISTRATION NUMBER: NCT02428062www.clinicaltrials.gov.

Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema.

OBJECTIVE: Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis. DESIGN: Laboratory investigation. SETTING: Animal unit. SUBJECTS: Thirty healthy piglets. INTERVENTIONS: Two groups of animals were ventilated for 54 hours with matched lung strains (ratio between tidal volume and functional residual capacity) but different lung strain rates (ratio between strain and inspiratory time). Individual strains ranged between 0.6 and 3.5 in both groups. Piglets ventilated with low strain rates had an inspiratory-to-expiratory time ratio of 1:2-1:3. Those ventilated with high strain rates had much lower inspiratory-to-expiratory time ratios (down to 1:9). Respiratory rate was always 15 breaths/min. Lung viscoelastic behavior, with ventilator setting required per protocol, was "quantified" as dynamic respiratory system hysteresis (pressure-volume loop [in Joules]) and stress relaxation (airway pressure drop during an end-inspiratory pause [in cm H2O]). Primary outcome was the occurrence of pulmonary edema within 54 hours. MEASUREMENTS AND MAIN RESULTS: On average, the two study groups were ventilated with well-matched strains (2.1 ± 0.9 vs 2.1 ± 0.9; p = 0.864) but different strain rates (1.8 ± 0.8 vs 4.6 ± 1.5 s; p < 0.001), dynamic respiratory system hysteresis (0.6 ± 0.3 vs 1.4 ± 0.8 J; p = 0.001), and stress relaxation (3.1 ± 0.9 vs 5.0 ± 2.3 cm H2O; p = 0.008). The prevalence of pulmonary edema was 20% among piglets ventilated with low strain rates and 73% among those ventilated with high strain rates (p = 0.010). CONCLUSIONS: High strain rate is a risk factor for ventilator-induced pulmonary edema, possibly because it amplifies lung viscoelastic behavior.

Mechanical Power and Development of Ventilator-induced Lung Injury.

BACKGROUND: The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. METHODS: Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. RESULTS: In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r = 0.41, P = 0.001) and lung elastance (r = 0.33, P < 0.01) and decrease in PaO2/FIO2 (r = 0.40, P < 0.001) at the end of the study. CONCLUSION: In piglets, VILI develops if a mechanical power threshold is exceeded.

Lung anatomy, energy load, and ventilator-induced lung injury.

BACKGROUND: High tidal volume can cause ventilator-induced lung injury (VILI), but positive end-expiratory pressure (PEEP) is thought to be protective. We aimed to find the volumetric VILI threshold and see whether PEEP is protective per se or indirectly. METHODS: In 76 pigs (22 ± 2 kg), we examined the lower and upper limits (30.9-59.7 mL/kg) of inspiratory capacity by computed tomography (CT) scan at 45 cmH2O pressure. The pigs underwent a 54-h mechanical ventilation with a global strain ((tidal volume (dynamic) + PEEP volume (static))/functional residual capacity) from 0.45 to 5.56. The dynamic strain ranged from 18 to 100 % of global strain. Twenty-nine pigs were ventilated with end-inspiratory volumes below the lower limit of inspiratory capacity (group "Below"), 38 within (group "Within"), and 9 above (group "Above"). VILI was defined as death and/or increased lung weight. RESULTS: "Below" pigs did not develop VILI; "Within" pigs developed lung edema, and 52 % died before the end of the experiment. The amount of edema was significantly related to dynamic strain (edema 188-153 × dynamic strain, R (2) = 0.48, p < 0.0001). In the "Above" group, 66 % of the pigs rapidly died but lung weight did not increase significantly. In pigs ventilated with similar tidal volume adding PEEP significantly increased mortality. CONCLUSIONS: The threshold for VILI is the lower limit of inspiratory capacity. Below this threshold, VILI does not occur. Within these limits, severe/lethal VILI occurs depending on the dynamic component. Above inspiratory capacity stress at rupture may occur. In healthy lungs, PEEP is protective only if associated with a reduced tidal volume; otherwise, it has no effect or is harmful.

Validation of computed tomography for measuring lung weight.

BACKGROUND: Lung weight characterises severity of pulmonary oedema and predicts response to mechanical ventilation. The aim of this study was to evaluate the accuracy of quantitative analysis of thorax computed tomography (CT) for measuring lung weight in pigs with or without pulmonary oedema. METHODS: Thirty-six pigs were mechanically ventilated with different tidal volumes and positive end-expiratory pressures that did or did not induce pulmonary oedema. After 54 h, they underwent thorax CT (CT in vivo ) and were then sacrificed and exsanguinated. Fourteen pigs underwent a second thorax CT (CTpost-exsang.) after exsanguination. Lungs were excised and weighed with a balance (balancepost-exsang.). Agreement between lung weights measured with the balance (considered as reference) and those estimated by quantitative analysis of CT was assessed with Bland-Altman plots. RESULTS: One animal unexpectedly died before CT in vivo . In 35 pigs, lung weight measured with balancepost-exsang. was 371 ± 184 g and that estimated with CT in vivo was 481 ± 189 g (p < 0.001). Bias between methods was -111 g (-35%) and limits of agreement were -176 (-63%) and -46 g (-8%). Measurement error was similar in animals with (-112 ± 45 g; n = 11) or without (-110 ± 27 g; n = 24) pulmonary oedema (p = 0.88). In 14 pigs with thorax CT after exsanguination, lung weight measured with balancepost-exsang. was 342 ± 165 g and that estimated with CTpost-exsang. was 352 ± 160 g (p = 0.02). Bias between methods was -9 g (-4%) and limits of agreement were -36 (-11%) and 17 g (3%). Measurement errors were similar in pigs with (-1 ± 26 g; n = 11) or without (-12 ± 7 g; n = 3) pulmonary oedema (p = 0.12). CONCLUSIONS: Compared to the balance, CT obtained in vivo constantly overestimated the lung weight, as it included pulmonary blood (whereas the balance did not). By contrast, CT obtained after exsanguination provided accurate and reproducible results.