Derek Sakata

Hypercapnic hyperventilation shortens emergence time from isoflurane anesthesia

BACKGROUND:To shorten emergence time after a procedure using volatile anesthesia, 78% of anesthesiologists recently surveyed used hyperventilation to rapidly clear the anesthetic from the lungs. Hyperventilation has not been universally adapted into clinical practice because it also decreases the Paco2, which decreases cerebral bloodflow and depresses respiratory drive. Adding deadspace to the patient’s airway may be a simple and safe method of maintaining a normal or slightly increased Paco2 during hyperventilation. METHODS:We evaluated the differences in emergence time in 20 surgical patients undergoing 1 MAC of isoflurane under mild hypocapnia (ETco2 approximately 28 mmHg) and mild hypercapnia (ETco2 approximately 55 mmHg). The minute ventilation in half the patients was doubled during emergence, and hypercapnia was maintained by insertion of additional airway deadspace to keep the ETco2 close to 55 mmHg during hyperventilation. A charcoal canister adsorbed the volatile anesthetic from the deadspace. Fresh gas flows were increased to 10 L/min during emergence in all patients. RESULTS:The time between turning off the vaporizer and the time when the patients opened their eyes and mouths, the time of tracheal extubation, and the time for normalized bispectral index to increase to 0.95 were faster whenever hypercapnic hyperventilation was maintained using rebreathing and anesthetic adsorption (P < 0.001). The time to tracheal extubation was shortened by an average of 59%. CONCLUSIONS:The emergence time after isoflurane anesthesia can be shortened significantly by using hyperventilation to rapidly clear the anesthetic from the lungs and CO2 rebreathing to induce hypercapnia during hyperventilation. The device should be considered when it is important to provide a rapid emergence, especially after surgical procedures where a high concentration of the volatile anesthetic was maintained right up to the end of the procedure, or where surgery ends abruptly and without warning.

Hypercapnia shortens emergence time from inhaled anesthesia in pigs.

BACKGROUND:Anesthetic clearance from the lungs and the circle rebreathing system can be maximized using hyperventilation and high fresh gas flows. However, the concomitant clearance of CO2 decreases PAco2, thereby decreasing cerebral blood flow and slowing the clearance of anesthetic from the brain. This study shows that in addition to hyperventilation, hypercapnia (CO2 infusion or rebreathing) is a significant factor in decreasing emergence time from inhaled anesthesia. METHODS:We anesthetized seven pigs with 2 MACPIG of isoflurane and four with 2 MACPIG of sevoflurane. After 2 h, anesthesia was discontinued, and the animals were hyperventilated. The time to movement of multiple limbs was measured under hypocapnic (end-tidal CO2 = 22 mm Hg) and hypercapnic (end-tidal CO2 = 55 mm Hg) conditions. RESULTS:The time between turning off the vaporizer and to movement of multiple limbs was faster with hypercapnia during hyperventilation. Emergence time from isoflurane and sevoflurane anesthesia was shortened by an average of 65% with rebreathing or with the use of a CO2 controller (P < 0.05). CONCLUSIONS:Hypercapnia, along with hyperventilation, may be used clinically to decrease emergence time from inhaled anesthesia. These time savings might reduce drug costs. In addition, higher PAco2 during emergence may enhance respiratory drive and airway protection after tracheal extubation.

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

Background Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isofluranes antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. Method Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. Results Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. Conclusions Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.

Rapid Recovery from Sevoflurane and Desflurane with Hypercapnia and Hyperventilation

BACKGROUND: Hypercapnia with hyperventilation shortens the time between turning off the vaporizer (1 MAC) and when patients open their eyes after isoflurane anesthesia by 62%. METHODS: In the present study we tested whether a proportional shortening occurs with sevoflurane and desflurane. RESULTS: Consistent with a proportional shortening, we found that hypercapnia with hyperventilation decreased recovery times by 52% for sevoflurane and 64% for desflurane (when compared with normal ventilation with normocapnia). CONCLUSION: Concurrent hyperventilation to rapidly remove the anesthetic from the lungs and rebreathing to induce hypercapnia can significantly shorten recovery times and produce the same proportionate decrease for anesthetics that differ in solubility.

Inhaled Remifentanil in Rodents.

BACKGROUND:Remifentanil is an injectable opioid that is metabolized rapidly at a constant rate by plasma esterases. This supports its use as an analgesic for short-term, but painful, procedures in a wide range of patients. The aim of this study was to explore the feasibility and safety of administering remifentanil via inhalation. Our hypothesis was that inhaled remifentanil would be absorbed rapidly, pharmacologically active, rapidly cleared, and noninjurious to rodent airways and lungs. METHODS:Rats were exposed to remifentanil aerosol (100–2000 &mgr;g/mL) for varying times (1–5 minutes). Analgesia was quantified as a function of dose and time by measuring time to tail flick in response to a painful stimulus. Remifentanil was measured in blood using liquid chromatography-tandem mass spectrometry. Pulmonary mechanics and histology were assessed in mice for the evidence of adverse effects after acute and repeated (subacute) dosing. RESULTS:Exposure of rats to remifentanil aerosols produced dose-dependent analgesia within 2 minutes, which was sustained for the exposure period. Subsequently, the rats experienced rapid and complete recovery with a return to baseline tail flick response to a painful stimulus within 5 minutes. Analgesia mirrored the concentration profile of remifentanil in blood, and the animals were not affected adversely by repeated dosing. Pulmonary mechanics measurements in mice indicated that remifentanil was nonirritating and that the nasal and respiratory tissues of rats were free of significant morphological changes. CONCLUSIONS:Remifentanil delivered by inhalation is rapidly absorbed, pharmacologically active, rapidly cleared, and noninjurious to respiratory tissues in rodents.

Inhaled Remimazolam Potentiates Inhaled Remifentanil in Rodents.

BACKGROUND: Remimazolam is an ester-based short-acting benzodiazepine currently in clinical trials for IV administration. This study explored the feasibility of delivering remimazolam alone and as an adjunct to remifentanil via inhalation in rodent models. METHODS: Mice were exposed to remimazolam via inhalation; sedation was assessed using time to movement outside a set perimeter. Rats were also exposed to remimazolam aerosol alone and in combination with inhaled remifentanil, and analgesia was quantified by using a tail flick meter. Pulmonary injury was assessed in mice using mechanics measurements. RESULTS: Mice showed significantly increased time to movement outside a set perimeter after 5-minute exposure to increasing concentrations (10–25 mg/mL solutions) of inhaled remimazolam aerosols. Differences in mean (95% confidence interval) time to movement from pretest baseline group (0.05 [0.01–0.09] minutes) were 11 (4–18), 15 (5–26), 30 (19–41), and 109 (103–115) minutes after exposure to remimazolam aerosol of 10, 15, 20, and 25 mg/mL, respectively (P = .007 – P < .0001). Exposure of rats to remimazolam aerosols alone failed to produce sedation or analgesia after a 5-minute exposure. When remimazolam (10 or 25 mg/mL) was administered in combination with 250 &mgr;g/mL remifentanil, there was a significant difference in time to tail flick (P < .0001) consistent with a strong analgesic effect. Mean (95% confidence interval) differences in time to tail flick from the pretest baseline group (3.2 [2.5–3.9] seconds) were 14 (10–18) seconds when 250 &mgr;g/mL remifentanil was administered with either 10 or 25 mg/mL remimazolam. Remimazolam alone or in combination with remifentanil did not cause lung irritation, bronchospasm, or other adverse pulmonary events to the respiratory tract of mice as assessed by Flexi-Vent pulmonary function tests. CONCLUSIONS: Remimazolam can significantly potentiate the analgesic effect of remifentanil when concurrently delivered via inhalation.

Propofol for Treatment-Resistant Depression: A Pilot Study

Abstract Background We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods Ten participants with moderate-to-severe medication-resistant depression (age 18–45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0–45 points), corresponding to a mean 58% improvement from baseline (range 0–100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol’s antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

A Turbine-Driven Ventilator Improves Adherence to Advanced Cardiac Life Support Guidelines During a Cardiopulmonary Resuscitation Simulation

BACKGROUND: Research has shown that increased breathing frequency during cardiopulmonary resuscitation is inversely correlated with systolic blood pressure. Rescuers often hyperventilate during cardiopulmonary resuscitation (CPR). Current American Heart Association advanced cardiac life support recommends a ventilation rate of 8–10 breaths/min. We hypothesized that a small, turbine-driven ventilator would allow rescuers to adhere more closely to advanced cardiac life support (ACLS) guidelines. METHODS: Twenty-four ACLS-certified health-care professionals were paired into groups of 2. Each team performed 4 randomized rounds of 2-min cycles of CPR on an intubated mannikin, with individuals altering between compressions and breaths. Two rounds of CPR were performed with a self-inflating bag, and 2 rounds were with the ventilator. The ventilator was set to deliver 8 breaths/min, pressure limit 22 cm H2O. Frequency, tidal volume (VT), peak inspiratory pressure, and compression interruptions (hands-off time) were recorded. Data were analyzed with a linear mixed model and Welch 2-sample t test. RESULTS: The median (interquartile range [IQR]) frequency with the ventilator was 7.98 (7.98–7.99) breaths/min. Median (IQR) frequency with the self-inflating bag was 9.5 (8.2–10.7) breaths/min. Median (IQR) ventilator VT was 0.5 (0.5–0.5) L. Median (IQR) self-inflating bag VT was 0.6 (0.5–0.7) L. Median (IQR) ventilator peak inspiratory pressure was 22 (22–22) cm H2O. Median (IQR) self-inflating bag peak inspiratory pressure was 30 (27–35) cm H2O. Mean ± SD hands-off times for ventilator and self-inflating bag were 5.25 ± 2.11 and 6.41 ± 1.45 s, respectively. CONCLUSIONS: When compared with a ventilator, volunteers ventilated with a self-inflating bag within ACLS guidelines. However, volunteers ventilated with increased variation, at higher VT levels, and at higher peak pressures with the self-inflating bag. Hands-off time was also significantly lower with the ventilator. (ClinicalTrials.gov registration NCT02743299.)