Elective Tracheal Intubation With the VieScope-A Prospective Randomized Non-inferiority Pilot Study (VieScOP-Trial).

Background: Tracheal intubation is commonly performed after direct laryngoscopy using Macintosh laryngoscopes (MacL), but visualization of the larynx may be inadequate. The VieScope (VSC) as a new type of laryngoscope consisting of a straight, shielded, illuminated tube used to perform intubation via a bougie was investigated in this prospective randomized trial in patients without expected difficult airways. Methods: With ethics approval, 2 × 29 patients for elective surgery were randomized 1:1 to intubation with VSC or MacL. Endpoints were first attempt success rates (FAS), Percentage of Glottis Opening Scale (POGO), time to intubation (TTI), and difficulty ratings on visual analog scales (0-100, lower values better). Data are given as mean ± standard deviation. Results: The FAS was 83 ± 38% for VSC and 86 ± 34% for MacL (P = 0.723). For VSC, POGO was 86 ± 17% and for MacL 68 ± 30% (P = 0.007). TTI for VSC was 93 ± 67s vs. 38 ± 17 for MacL (P < 0.001). Difficulty of intubation was rated 23 ± 22 for VSC vs. 18 ± 22 for MacL (P = 0.422), viewing conditions 12 ± 15 vs. 24 ± 25 (P = 0.031), and difficulty of tube placement was rated 27 ± 30 vs. 7 ± 8 (P = 0.001). Conclusion: No difference in FAS was detected between VSC and MacL. Visualization of the larynx was superior using the VSC, while TTI was prolonged and tube placement via bougie was more challenging. The VSC could be an alternative to MacL in patients with difficult laryngoscopy, but this should be investigated further in patients with expected difficult airways.

Tracheal Tube-Mounted Camera Assisted Intubation vs. Videolaryngoscopy in Expected Difficult Airway: A Prospective, Randomized Trial (VivaOP Trial).

Background: Tracheal intubation in patients with an expected difficult airway may be facilitated by videolaryngoscopy (VL). The VL viewing axis angle is specified by the blade shape and visualization of the larynx may fail if the angle does not meet anatomy of the patient. A tube with an integrated camera at its tip (VST, VivaSight-SL) may be advantageous due to its adjustable viewing axis by means of angulating an included stylet. Methods: With ethics approval, we studied the VST vs. VL in a prospective non-inferiority trial using end-tidal oxygen fractions (etO2) after intubation, first-attempt success rates (FAS), visualization assessed by the percentage of glottis opening (POGO) scale, and time to intubation (TTI) as outcome parameters. Results: In this study, 48 patients with a predicted difficult airway were randomized 1:1 to intubation with VST or VL. Concerning oxygenation, the VST was non-inferior to VL with etO2 of 0.79 ± 0.08 (95% CIs: 0.75-0.82) vs. 0.81 ± 0.06 (0.79-0.84) for the VL group, mean difference 0.02 (-0.07 to 0.02), p = 0.234. FAS was 79% for VST and 88% for VL (p = 0.449). POGO was 89 ± 21% in the VST-group and 60 ± 36% in the VL group, p = 0.002. TTI was 100 ± 57 s in the VST group and 68 ± 65 s in the VL group (p = 0.079). TTI with one attempt was 84 ± 31 s vs. 49 ± 14 s, p < 0.001. Conclusion: In patients with difficult airways, tracheal intubation with the VST is feasible without negative impact on oxygenation, improves visualization but prolongs intubation. The VST deserves further study to identify patients that might benefit from intubation with VST.

Airway management and perioperative adverse events in children with mucopolysaccharidoses and mucolipidoses: A retrospective cohort study.

BACKGROUND: Children suffering from mucopolysaccharidoses (subtypes I, II, III, IV, VI, and VII) or mucolipidoses often require anesthesia, but are at high risk for perioperative adverse events. However, the impact of the disease subtype and the standard of care for airway management are still unclear. AIMS: This study aimed to assess independent risk factors for perioperative adverse events in individuals with mucopolysaccharidoses/mucolipidoses and to analyze the interaction with the primary airway technique implemented. METHODS: This retrospective study included individuals with mucopolysaccharidoses/mucolipidoses who underwent anesthesia at two high-volume centers from 2002 to 2016. The data were analyzed in a multivariate hierarchical model, accounting for repeated anesthesia procedures within the same patient and for multiple events within a single anesthesia. RESULTS: Of 141 identified inpatients, 67 (63 mucopolysaccharidoses and 4 mucolipidoses) underwent 269 anesthesia procedures (study cases) for 353 surgical or diagnostic interventions. At least one perioperative adverse event occurred in 25.6% of the cases. The risk for perioperative adverse events was higher in mucopolysaccharidoses type I (OR 8.0 [1.5-42.7]; P = .014) or type II (OR 8.8 [1.3-58.6]; P = .025) than in type III. Fiberoptic intubation through a supraglottic airway was associated with the lowest risk for perioperative adverse events and lowest conversion rate. Direct laryngoscopy was associated with a significantly higher risk for airway management problems than indirect techniques (estimated event rates 47.8% vs 10.1%, OR 24.05 [5.20-111.24]; P < .001). The risk for respiratory adverse events was significantly higher for supraglottic airway (22.6%; OR 31.53 [2.79-355.88]; P = .001) and direct laryngoscopy (14.8%; OR 14.70 [1.32-163.44]; P = .029) than for fiberoptic intubation through a supraglottic airway (2.1%). CONCLUSIONS: The disease subtype and primary airway technique were the most important independent risk factors for perioperative adverse events. Our findings indicate that in MPS/ML children with predicted difficult airway indirect techniques should be favored for the first tracheal intubation attempt.

Assessment of central hemodynamic effects of phenylephrine: an animal experiment.

Phenylephrine is an α1-adrenergic receptor agonist widely used to treat perioperative hypotension. Its other hemodynamic effects, in particular on preload and contractility, remain controversial. We, therefore, investigated the effect of continuously applied phenylephrine on central hemodynamics in eight mechanically ventilated domestic pigs. Mean arterial pressure (MAP) was increased in steps by 50%, and 100% using phenylephrine. Besides stroke volume (SV), cardiac output (CO), and MAP, mean systemic vascular resistance (SVR) and dynamic arterial elastance (Eadyn) were assessed for characterization of afterload. Changes in preload were assessed by central venous pressure (CVP), global end-diastolic volume (GEDV), mean systemic filling pressure analog (Pmsfa), pulse pressure variation (PPV), and stroke volume variation (SVV). Further, cardiac function index (CFI), global ejection fraction and dPmax were measured as markers of preload dependent contractility. MAP, SV, and CO significantly increased following both interventions, as did SVR. In contrast, Eadyn did not show significant changes. Although the volumetric preload variable GEDV increased after the first step of phenylephrine, this was not reflected by significant changes in CVP or Pmsfa. CFI and dPmax significantly increased after both steps. Phenylephrine does not only affect cardiac afterload, but also increases effective preload. In contrast to CVP and Pmsfa, this effect can be monitored by GEDV. Further, phenylephrine affects contractility.

Anesthetic considerations for patients with esophageal achalasia undergoing peroral endoscopic myotomy: a retrospective case series review.

PURPOSE: Peroral endoscopic myotomy (POEM) is a novel technique for treating esophageal achalasia. During POEM, carbon dioxide (CO2) is insufflated to aid surgical dissection, but it may inadvertently track into surrounding tissues, causing systemic CO2 uptake and tension capnoperitoneum. This in turn may affect cardiorespiratory function. This study quantified these cardiorespiratory effects and treatment by hyperventilation and percutaneous abdominal needle decompression (PND). METHODS: One hundred and seventy-three consecutive patients who underwent POEM were included in this four-year retrospective study. Procedure-related changes in peak inspiratory pressure (pmax), end-tidal CO2 levels (etCO2), minute ventilation (MV), mean arterial pressure (MAP), and heart rate (HR) were analyzed. We also quantified the impact of PND on these cardiorespiratory parameters. RESULTS: During the endoscopic procedure, cardiorespiratory parameters increased from baseline: pmax 15.1 (4.5) vs 19.8 (4.7) cm H2O; etCO2 4.5 (0.4) vs 5.5 (0.9) kPa [34.0 (2.9) vs 41.6 (6.9) mmHg]; MAP 73.9 (9.7) vs 99.3 (15.2) mmHg; HR 67.6 (12.4) vs 85.3 (16.4) min-1 (P < 0.001 for each). Hyperventilation [MV 5.9 (1.2) vs 9.0 (1.8) L·min-1, P < 0.001] was applied to counteract iatrogenic hypercapnia. Individuals with tension capnoperitoneum treated with PND (n = 55) had higher peak pmax values [22.8 (5.7) vs 18.4 (3.3) cm H2O, P < 0.001] than patients who did not require PND. After PND, pmax [22.8 (5.7) vs 19.9 (4.3) cm H2O, P = 0.045] and MAP [98.2 (16.3) vs 88.6 (11.8) mmHg, P = 0.013] decreased. Adverse events included pneumothorax (n = 1), transient myocardial ischemia (n = 1), and subcutaneous emphysema (n = 49). The latter precluded immediate extubation in eight cases. Postanesthesia care unit (PACU) stay was longer in individuals with subcutaneous emphysema than in those without [74.9 min (34.5) vs 61.5 (26.8 min), P = 0.007]. CONCLUSION: Carbon dioxide insufflation during POEM produces systemic CO2 uptake and increased intra-abdominal pressure. Changes in cardiorespiratory parameters include increased pmax, etCO2, MAP, and HR. Hyperventilation and PND help mitigate some of these changes. Subcutaneous emphysema is common and may delay extubation and prolong PACU stay.

The effect of a checklist on the quality of patient handover from the operating room to the intensive care unit: A randomized controlled trial.

PURPOSE: Handover of patient care is a potential safety risk for the patient due to loss of information which may result in adverse outcome. We hypothesized that a checklist for handover from the operating room (OR) to the intensive care unit (ICU) will lead to an increase of quality regarding information transfer compared with a nonstandardized handover procedure. MATERIALS AND METHODS: The study was conducted as a prospective, randomized trial in a university hospital. The quality of handovers with checklist was compared with handovers without checklist. Handovers were recorded by digital voice recorder and analyzed using an individual rating sheet for each patient. This enabled to discriminate between items that "must be handed over" (red items) and items that "should be handed over" (yellow items). RESULTS: A total of 121 patient handovers from OR to ICU were included. Significantly more red items were handed over in the study group compared with the control group (study group: median 87.1%, 25-27 percentile 77.1%-90.0%; control group: median 75.0%, 25-75 percentile 66.7%-88.6%; P < .01). CONCLUSIONS: This study gives first evidence that the use of a standardized checklist for patient handover from OR to ICU increases the quantity and quality of transmitted medical information.

Lipophilic and stereospecific interactions of amino-amide local anesthetics with human Kv1.1 channels.

BACKGROUND: This study's aim was to investigate the interaction of amino-amide local anesthetics with human Kv1.1 potassium channels. These channels were chosen because of their proven physiologic role. By using a homolog series of local anesthetics with different lengths of the N-substituent, it was intended to elucidate the role of lipophilic interactions with Kv1.1. The use of stereoisomers allowed testing of the role of polar drug actions. METHODS: Human Kv1.1 channels were measured with the patch clamp technique. Concentration-response data were described by Hill functions. Gating changes were described by Boltzmann functions. RESULTS: Inhibition of Kv1.1 channels by dextrobupivacaine, bupivacaine, levobupivacaine, dextroropivacaine, levoropivacaine, and mepivacaine was concentration dependent, reversible, stereoselective, voltage dependent, and frequency independent. The IC(50) values were (mean +/- SEM) 41 +/- 3 microm (n = 20), 56 +/- 3 microm (n = 26), 76 +/- 8 microm (n = 24), 135 +/- 29 microm (n = 23), 313 +/- 32 microm (n = 25), and 1,451 +/- 351 microm (n = 23), respectively. The midpoint of current activation was shifted into the hyperpolarizing direction. The inhibitory potency as well as the potency to induce gating changes correlated with the number of CH(2) groups in the side chain of the drugs (r > 0.9, P < 0.05). CONCLUSIONS: Kv1.1 channels constitute an important biophysical model for elucidating molecular mechanisms underlying local anesthetic drug effects. Inhibition likely results from an open state-dependent blocking mechanism. Interaction of local anesthetics with the ion channel protein is determined by lipophilic drug properties.

Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.

BACKGROUND: Kv1.1 and Kv7.2/7.3 channels control excitability of neuronal cells. As hyperexcitability is a sign of neuropathic pain, epilepsy, and anxiety disorders, these channels may be important molecular targets of amitriptyline that cause pharmacological as well as toxicological effects by altering neuronal excitability. Since the molecular mechanisms underlying these effects of amitriptyline have not been fully elucidated, we aimed to characterize the interaction of amitriptyline with human Kv1.1 and Kv7.2/7.3 channels. We also intended to establish the interaction of amitriptyline with the Kv7.2/7.3 channel opener, retigabine. METHODS: Kv1.1 and Kv7.2/7.3 channels were expressed in human embryonic kidney cells and in Chinese hamster ovary cells. The effects of amitriptyline and retigabine were studied with the patch-clamp technique. RESULTS: Amitriptyline inhibited Kv1.1 and Kv7.2/7.3 channels in a concentration-dependent and reversible manner. The IC50-value was 22 +/- 3 microM (n = 33) and 10 +/- 1 microM (n = 40), respectively. Deactivating inward currents of Kv7.2/7.3 channels were inhibited with an IC50-value of 4.2 +/- 0.6 microM (n = 32). Inhibition of Kv7.2/7.3 channels by amitriptyline reversibly depolarized the resting membrane potential. Retigabine reversed both the inhibitory action of amitriptyline on Kv7.2/7.3 channels as well as the depolarization of the membrane potential. CONCLUSIONS: Since amitriptyline inhibited Kv1.1 and Kv7.2/7.3 channels only at toxicologically relevant plasma concentrations, our results suggest a role for these channels in the neuroexcitatory side effects of amitriptyline. As the inhibitory effects of amitriptyline were reversed by retigabine, a combination of amitriptyline and retigabine could be of additional benefit in the therapy of neuropathic pain.

Retigabine stimulates human KCNQ2/Q3 channels in the presence of bupivacaine.

BACKGROUND: Inhibition of KCNQ2/Q3 channels may cause convulsion in humans. The interaction of bupivacaine with these channels is unknown. The anticonvulsant retigabine activates KCNQ2/Q3 channels and may reverse inhibitory actions of bupivacaine. Potassium channel stimulation may thus constitute a novel approach to treat local anesthetic-induced seizures. The aim of this study was to characterize bupivacaine effects on KCNQ2/Q3 channels and to investigate whether retigabine reverses the effects of the local anesthetic. METHODS: KCNQ2/Q3 channels were transiently expressed in Chinese hamster ovary cells. The effects of bupivacaine and retigabine were studied with the patch-clamp technique. RESULTS: Bupivacaine inhibited KCNQ2/Q3 channels in a concentration-dependent and reversible manner. The concentration-response curve was described by a Hill equation (IC50 = 173 +/- 7 microm, Hill coefficient = 1.4 +/- 0.1, mean +/- SEM, n = 37). The inhibitory effect did not differ between bupivacaine and levobupivacaine (42 +/- 4%, n = 7, versus 42 +/- 5%, n = 10; P > 0.05). Ropivacaine was four times less potent than bupivacaine. The inhibition of KCNQ2/Q3 channels by bupivacaine resulted in a significant and reversible depolarization of the membrane potential. Retigabine (300 nm-10 microm) reversed the inhibitory action of bupivacaine on KCNQ2/Q3 channels as well as the depolarization of the membrane potential. CONCLUSIONS: The anticonvulsant retigabine at nanomolar concentrations reverses the inhibitory effect of micromolar concentrations of bupivacaine. Our results allow the hypothesis that activation of KCNQ2/Q3 channels by retigabine may offer a novel therapeutic approach for the treatment of bupivacaine-induced seizures.

Inhibition of human TREK-1 channels by bupivacaine.

UNLABELLED: Human TWIK-related K(+) channels (TREK-1) stabilize the membrane potential (mp) of neurons and have a major role in the regulation of membrane excitability. In view of their physiological significance, interaction of bupivacaine with TREK-1 channels may be clinically important. Our aim was to characterize with the patch-clamp technique the properties of human TREK-1 channels and the effects of bupivacaine on these channels expressed in Chinese hamster ovary (CHO) cells. Transfection of CHO cells with TREK-1 channels (CHO(TREK-1) cells) hyperpolarized the mp from -33 +/- 13 to -78 +/- 4 mV. The channels were stimulated by intracellular acidosis. Inhibition of TREK-1 channels by bupivacaine was reversible, concentration-dependent, voltage-independent, and increased with intracellular acidosis. Bupivacaine depolarized the mp of CHO(TREK-1) cells in a reversible and concentration-dependent manner. Concentrations for channel inhibition and membrane depolarization were not linearly related (50% inhibitory concentration value for channel inhibition 370 +/- 20 micro M, Hill coefficient 1.8 +/- 0.1, n = 51; 50% inhibitory concentration value for membrane depolarization 856 +/- 14 micro M, Hill coefficient 2.4 +/- 0.1, mean +/- SEM, n = 27). The results suggest that protonated bupivacaine elicits the observed effects via a site of interaction accessible from the intracellular space. Inhibition of TREK-1 channels and consecutive depolarization of the cell membrane by bupivacaine may contribute to blockade of neuronal signal conduction during regional anesthesia. IMPLICATIONS: The interaction of bupivacaine with human TREK-1 channels was studied with the patch-clamp technique. Bupivacaine inhibited TREK-1 channels and depolarized the membrane potential of cells expressing TREK-1 channels in a concentration-dependent and reversible manner. Both effects may contribute to conductance block caused by bupivacaine.

Molecular site of action of the antiarrhythmic drug propafenone at the voltage-operated potassium channel Kv2.1.

The effects of the antiarrhythmic drug propafenone at Kv2.1 channels were studied with wild-type and mutated channels expressed in Xenopus laevis oocytes. Propafenone decreased the Kv2.1 currents in a time- and voltage-dependent manner (decrease of the time constants of current rise, increase of block with the duration of voltage steps starting from a block of less than 19%, increase of block with the amplitude of depolarization yielding a fractional electrical distance delta of 0.11 to 0.16). Block of Kv2.1 appeared with application to the intracellular, but not the extracellular, side of membrane patches. In mutagenesis experiments, all parts of the Kv2.1 channel were successively exchanged with those of the Kv1.2 channel, which is much more sensitive to propafenone. The intracellular amino and carboxyl terminus and the intracellular linker S4-S5 reduced the blocking effect of propafenone, whereas the linker S5-S6, as well as the segment S6 of the Kv1.2 channel, abolished it to the value of the Kv1.2 channel. In the linker S5-S6, this effect could be narrowed down to two groups of amino acids (groups 372 to 374 and 383 to 384), which also affected the sensitivity to tetraethylammonium. In segment S6, several amino acids in the intracellularly directed part of the helix significantly reduced propafenone sensitivity. The results suggest that propafenone blocks the Kv2.1 channel in the open state from the intracellular side by entering the inner vestibule of the channel. These results are consistent with a direct interaction of propafenone with the lower part of the pore helix and/or residues of segment S6.