Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial.

BACKGROUND: Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit (SICU). Attempts to mobilise critically ill patients early after surgery are frequently restricted, but we tested whether early mobilisation leads to improved mobility, decreased SICU length of stay, and increased functional independence of patients at hospital discharge. METHODS: We did a multicentre, international, parallel-group, assessor-blinded, randomised controlled trial in SICUs of five university hospitals in Austria (n=1), Germany (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been mechanically ventilated for <48 h, and were expected to require mechanical ventilation for ≥24 h) were randomly assigned (1:1) by use of a stratified block randomisation via restricted web platform to standard of care (control) or early, goal-directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score (SOMS) algorithm (intervention), which describes patients' mobilisation capacity on a numerical rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three main outcomes hierarchically tested in a prespecified order: the mean SOMS level patients achieved during their SICU stay (primary outcome), and patient's length of stay on SICU and the mini-modified functional independence measure score (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered with ClinicalTrials.gov (NCT01363102). FINDINGS: Between July 1, 2011, and Nov 4, 2015, we randomly assigned 200 patients to receive standard treatment (control; n=96) or intervention (n=104). Intention-to-treat analysis showed that the intervention improved the mobilisation level (mean achieved SOMS 2·2 [SD 1·0] in intervention group vs 1·5 [0·8] in control group, p<0·0001), decreased SICU length of stay (mean 7 days [SD 5-12] in intervention group vs 10 days [6-15] in control group, p=0·0054), and improved functional mobility at hospital discharge (mmFIM score 8 [4-8] in intervention group vs 5 [2-8] in control group, p=0·0002). More adverse events were reported in the intervention group (25 cases [2·8%]) than in the control group (ten cases [0·8%]); no serious adverse events were observed. Before hospital discharge 25 patients died (17 [16%] in the intervention group, eight [8%] in the control group). 3 months after hospital discharge 36 patients died (21 [22%] in the intervention group, 15 [17%] in the control group). INTERPRETATION: Early, goal-directed mobilisation improved patient mobilisation throughout SICU admission, shortened patient length of stay in the SICU, and improved patients' functional mobility at hospital discharge. FUNDING: Jeffrey and Judy Buzen.

A Comparison of Web-Based with Traditional Classroom-Based Training of Lung Ultrasound for the Exclusion of Pneumothorax.

BACKGROUND: Lung ultrasound (LUS) is a well-established method that can exclude pneumothorax by demonstration of pleural sliding and the associated ultrasound artifacts. The positive diagnosis of pneumothorax is more difficult to obtain and relies on detection of the edge of a pneumothorax, called the "lung point." Yet, anesthesiologists are not widely taught these techniques, even though their patients are susceptible to pneumothorax either through trauma or as a result of central line placement or regional anesthesia techniques performed near the thorax. In anticipation of an increased training demand for LUS, efficient and scalable teaching methods should be developed. In this study, we compared the improvement in LUS skills after either Web-based or classroom-based training. We hypothesized that Web-based training would not be inferior to "traditional" classroom-based training beyond a noninferiority limit of 10% and that both would be superior to no training. Furthermore, we hypothesized that this short training session would lead to LUS skills that are similar to those of ultrasound-trained emergency medicine (EM) physicians. METHODS: After a pretest, anesthesiologists from 4 academic teaching hospitals were randomized to Web-based (group Web), classroom-based (group class), or no training (group control) and then completed a posttest. Groups Web and class returned for a retention test 4 weeks later. All 3 tests were similar, testing both practical and theoretical knowledge. EM physicians (group EM) performed the pretest only. Teaching for group class consisted of a standardized PowerPoint lecture conforming to the Consensus Conference on LUS followed by hands-on training. Group Web received a narrated video of the same PowerPoint presentation, followed by an online demonstration of LUS that also instructs the viewer to perform an LUS on himself using a clinically available ultrasound machine and submit smartphone snapshots of the resulting images as part of a portfolio system. Group Web received no other hands-on training. RESULTS: Groups Web, class, control, and EM contained 59, 59, 20, and 42 subjects. After training, overall test results of groups Web and class improved by a mean of 42.9% (±18.1% SD) and 39.2% (±19.2% SD), whereas the score of group control did not improve significantly. The test improvement of group Web was not inferior to group class. The posttest scores of groups Web and class were not significantly different from group EM. In comparison with the posttests, the retention test scores did not change significantly in either group. CONCLUSIONS: When training anesthesiologists to perform LUS for the exclusion of pneumothorax, we found that Web-based training was not inferior to traditional classroom-based training and was effective, leading to test scores that were similar to a group of clinicians experienced in LUS.

The Mechanism of Mitral Regurgitation Influences the Temporal Dynamics of the Vena Contracta Area as Measured with Color Flow Doppler.

BACKGROUND: In patients with mitral regurgitation (MR), the effective regurgitant orifice area can be estimated by measuring the vena contracta area (VCA). We hypothesize that the VCA has characteristic temporal dynamics related to the underlying mechanism of functional mitral regurgitation (FMR) versus degenerative mitral valve disease (DMVD). METHODS: VCA measurements obtained by planimetry of the proximal jet from 3D transesophageal echocardiographic (TEE) color flow Doppler data sets were acquired in 42 cardiac surgical patients, including 22 with FMR and 20 with DMVD. Serial VCAs were measured throughout systole for each patient to evaluate variation in the effective regurgitant orifice area. Tercile averages were compared within and between the FMR and DMVD groups using repeated measures analysis of variance. Pairwise tests were Bonferroni-corrected for the number of comparisons. RESULTS: Normalized average VCA values in patients with FMR revealed a biphasic pattern compared with a monophasic pattern in patients with DMVD. Among FMR patients, normalized average VCA values in early (1.10 ± 0.32 cm2) and late systole (1.11 ± 0.33 cm2) were similar but were both significantly greater compared with mid-systole (0.79 ± 0.22 cm; P = 0.0144 and P = 0.0106, respectively). Among DMVD patients, normalized average VCA values in mid-systole (1.37 ± 0.15 cm2) were significantly greater than those in early (0.53 ± 0.14 cm2) and late systole (1.09 ± 0.18 cm2; P < 0.0001 for both). An analysis of normalized average VCAs also revealed significant differences between the FMR and the DMVD groups during early (1.10 ± 0.32 cm vs 0.53 ± 0.14 cm2) and mid-systole (0.79 ± 0.22 cm2 vs 1.37 ± 0.15 cm2; P < 0.0001 for both). CONCLUSIONS: VCA dynamics are governed by the mechanism of MR and are observed in FMR patients primarily as a biphasic temporal pattern compared with a monophasic temporal pattern in patients with DMVD.

Utility of intraoperative lung ultrasonography.

A patient with an endobronchial tumor and critical airway obstruction developed hypoxia and hypercarbia and, subsequently, cardiac arrest during a palliative laser core-out excision. The differential diagnosis included tension pneumothorax, as well as airway obstruction due to swelling of residual tumor or to blood clots. In this case, empiric needle decompression could have had deleterious consequences. Immediate bedside lung ultrasonography provided real-time information leading to the stabilization of the patient. This case provides compelling motivation for anesthesiologists to acquire this easily learned skill.

Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin - a model-based study.

PURPOSE: Dabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. PATIENTS AND METHODS: In a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. RESULTS: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups. CONCLUSION: Patients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin.

Adaptive control of bivalirudin in the cardiac intensive care unit.

Bivalirudin is a direct thrombin inhibitor used in the cardiac intensive care unit when heparin is contraindicated due to heparin-induced thrombocytopenia. Since it is not a commonly used drug, clinical experience with its dosing is sparse. In earlier work [1], we developed a dynamic system model that accurately predicts the effect of bivalirudin given dosage over time and patient physiological characteristics. This paper develops adaptive dosage controllers that regulate its effect to desired levels. To that end, and in the case that bivalirudin model parameters are available, we develop a Model Reference Control law. In the case that model parameters are unknown, an indirect Model Reference Adaptive Control scheme is applied to estimate model parameters first and then adapt the controller. Alternatively, direct Model Reference Adaptive Control is applied to adapt the controller directly without estimating model parameters first. Our algorithms are validated using actual patient data from a large hospital in the Boston area.

Providing initial transthoracic echocardiography training for anesthesiologists: simulator training is not inferior to live training.

OBJECTIVE: Transthoracic echocardiography (TTE) is finding increased use in anesthesia and critical care. Efficient options for training anesthesiologists should be explored. Simulator mannequins allow for training of manual acquisition and image recognition skills and may be suitable due to ease of scheduling. The authors tested the hypothesis that training with a simulator would not be inferior to training using a live volunteer. DESIGN: Prospective, randomized trial. SETTING: University hospital. PARTICIPANTS: Forty-six anesthesia residents, fellows, and faculty. INTERVENTIONS: After preparation with a written and video tutorial, study subjects received 80 minutes of TTE training using either a simulator or live volunteer. Practical and written tests were completed before and after training to assess improvement in manual image acquisition skills and theoretic knowledge. The written test was repeated 4 weeks later. MEASUREMENTS AND MAIN RESULTS: Performance in the practical image-acquisition test improved significantly after training using both the live volunteer and the simulator, improving by 4.0 and 4.3 points out of 15, respectively. Simulator training was found not to be inferior to live training, with a mean difference of -0.30 points and 95% confidence intervals that did not cross the predefined non-inferiority margin. Performance in the written retention test also improved significantly immediately after training for both groups but declined similarly upon repeat testing 4 weeks later. CONCLUSIONS: When providing initial TTE training to anesthesiologists, training using a simulator was not inferior to using live volunteers.

Predicting and evaluating the effect of bivalirudin in cardiac surgical patients.

Bivalirudin, used in patients with heparin-induced thrombocytopenia, is a direct thrombin inhibitor. Since it is a rarely used drug, clinical experience with its dosing is sparse. We develop two approaches to predict the Partial Thromboplastin Time (PTT) based on bivalirudin infusion rates. The first approach is model free and utilizes regularized regression. It is flexible enough to be used as predictors bivalirudin infusion rates measured over several time instances before the time at which a PTT prediction is sought. The second approach is model based and proposes a specific model for obtaining PTT which uses a shorter history of the past measurements. We learn population-wide model parameters by solving a nonlinear optimization problem. We also devise an adaptive algorithm based on the extended Kalman filter that can adapt model parameters to individual patients. The latter adaptive model emerges as the most promising as it yields reduced mean error compared to the model-free approach. The model accuracy we demonstrate on actual patient measurements is sufficient to be useful in guiding the optimal therapy.

Airway ventilation pressures during bronchoscopy, bronchial blocker, and double-lumen endotracheal tube use: an in vitro study.

OBJECTIVE: To quantify inspiratory flow resistance of instrumented single-lumen and double-lumen endotracheal tubes. DESIGN: Bench-top in vitro experiments. SETTING: Laboratory of a university hospital. PARTICIPANTS: In vitro lung simulator. INTERVENTIONS: A lung simulator was ventilated mechanically via several single- and double-lumen endotracheal tubes (ETT) that were instrumented with adult and pediatric bronchoscopes as well as bronchial blockers. While ventilating with a square-flow wave and increasing peak inspiratory flow from 10-100 L/min, the pressures proximal and distal to the instrumented ETT were measured. Flow (Q) and the pressure loss (∆P) were related with regression of the quadratic equation: ∆P=k1Q+k2Q2. MEASUREMENTS AND MAIN RESULTS: With all combinations of single-lumen endotracheal tubes, double-lumen endotracheal tubes, bronchial blockers, and adult and pediatric bronchoscopes, ∆P was accurately related to Q using the quadratic equation with excellent fit, R2>0.99 for all combinations. The regression parameters k1 and k2 were statistically significant for all combinations except k1 with a bronchoscope through 37-Fr double-lumen endotracheal tube. Parameter k2 was dominant at flows above 10 L/min for uninstrumented airways and 20 L/min for instrumented airways. ∆P increased dramatically with flow, and increased with decreasing endotracheal tube size or addition of instrumentation in a quantitatively predictable manner. CONCLUSIONS: Pressure loss across instrumented endotracheal tubes follows a predictable flow-dependant quadratic pattern. Using the quantitative in vitro results of this study, a clinician can maximize inspiratory ventilation pressures during these situations without delivering excessive airway pressures to the patient.

A Predictive Model for the Anticoagulant Bivalirudin Administered to Cardiac Surgical Patients.

Bivalirudin is used in patients with heparin-induced thrombocytopenia and is a direct thrombin inhibitor. Since it is a rarely used drug, clinical experience with its dosing is sparse. We develop a model that predicts the effect of bivalirudin, measured by the Partial Thromboplastin Time (PTT), based on its past fusion rates. We learn population-wide model parameters by solving a nonlinear optimization problem that uses a training set of patient data. More interestingly, we devise an adaptive algorithm based on the extended Kalman filter that can adapt model parameters to individual patients. The latter adaptive model emerges as the most promising as it reduces both the mean error and, drastically, the per-patient error variance. The model accuracy we demonstrate on actual patient measurements is sufficient to be useful in guiding optimal therapy.

Perioperative management of face transplantation: a survey.

BACKGROUND: Since the first facial allograft transplantation was reported in France in 2005, 18 cases have been performed in 4 countries and the rate is increasing. METHODS: We have devised a survey to assess anesthesia-related management and rationale of facial allograft transplantation. It was sent to the lead anesthesiologists of the first 14 face transplants performed worldwide. RESULTS: Responses were received corresponding to 13 face transplants. The median duration of surgery and anesthesia was 19 hours (95% confidence interval 15-23 hours). The surgical preparation and dissection of multiple small anatomical structures of the recipient was time-consuming for 11 cases. Blood loss was considerable. All patients received packed red blood cells (median 20 U, 95% confidence interval 5-28 U). A median of 13 L of crystalloid was administered (95% confidence interval 10-18 L). CONCLUSIONS: During facial allograft transplantation, the anesthesiologist must be prepared for a long anesthetic with rapid blood loss after reperfusion of the graft.

Three patients with full facial transplantation.

Unlike conventional reconstruction, facial transplantation seeks to correct severe deformities in a single operation. We report on three patients who received full-face transplants at our institution in 2011 in operations that aimed for functional restoration by coaptation of all main available motor and sensory nerves. We enumerate the technical challenges and postoperative complications and their management, including single episodes of acute rejection in two patients. At 6 months of follow-up, all facial allografts were surviving, facial appearance and function were improved, and glucocorticoids were successfully withdrawn in all patients.

Perioperative management of partial face transplantation involving a heparin antibody-positive donor.

Heparin-induced thrombocytopenia (HIT) is an immunologic condition that may lead to thrombosis. We present a case of face transplantation from a donor who had suffered a severe stroke, possibly from HIT, during cardiac surgery. The procedure was planned to include full heparinization. The anesthesia team was involved in the early planning phase and had detailed access to the donor's medical history; alternative anticoagulation for the donor and recipient was suggested so as to avoid a possible complication.

Modeling the effects of bivalirudin in cardiac surgical patients.

Bivalirudin is direct thrombin inhibitor used in patients with heparin-induced thrombocytopenia. A pharmacokinetic and--dynamic model that predicts the partial thromboplastin time (PTT) based on the past infusion rates of bivalirudin following dose adjustment would be useful to guide optimal therapy. In this retrospective study we randomized 132 patients to a derivation and a validation cohort, and tested two models. The first model is a single-state linear model; the other incorporates a non-linear element to account for renal elimination of bivalirudin. Both models predicted PTT changes equally well with root-mean squared errors of 15 to 16 seconds (Pearson correlation coefficients for both were 0.67). Intra- and inter-individual variability of response to bivalirudin was significant. Although a high percentage of patients had moderate to severe renal dysfunction at one point during the bivalirudin infusion, the non-linear model that incorporates variable renal clearance of drug did not perform better than the linear model. This finding persisted even in the subgroup analysis of patients with moderate and low estimated glomerular filtration rates.

Cardiac output monitoring using indicator-dilution techniques: basics, limits, and perspectives.

The ability to monitor cardiac output is one of the important cornerstones of hemodynamic assessment for managing critically ill patients at increased risk for developing cardiac complications, and in particular in patients with preexisting cardiovascular comorbidities. For >30 years, single-bolus thermodilution measurement through a pulmonary artery catheter for assessment of cardiac output has been widely accepted as the "clinical standard" for advanced hemodynamic monitoring. In this article, we review this clinical standard, along with current alternatives also based on the indicator-dilution technique, such as the transcardiopulmonary thermodilution and lithium dilution techniques. In this review, not only the underlying technical principles and the unique features but also the limitations of each application of indicator dilution are outlined.

Anesthesia for patients with severe chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Patients with chronic obstructive lung disease experience an increased risk of perioperative pulmonary complications. This review presents an evidence-based approach to perioperative care designed to optimize management. RECENT FINDINGS: Recent research has provided guidance regarding intraoperative and postoperative administration of oxygen and the selective use of volatile agents. The significance of preoperative malnutrition and postoperative epidural analgesia on outcomes has also been explored further. The opportunity for anesthesiologists to engage in tobacco interventions and the benefits of addressing smoking cessation have been studied. SUMMARY: Optimization for surgery includes preoperative treatment of reversible airway obstruction and respiratory infections, smoking cessation, and possibly nutritional interventions. Meticulous intraoperative monitoring combined with a sound understanding of pathophysiological mechanisms underlying air trapping will help clinicians strike a balance between permissive hypercapnia and adequate ventilation.

Time-dependent block and resurgent tail currents induced by mouse beta4(154-167) peptide in cardiac Na+ channels.

Resurgent tail Na(+) currents were first discovered in cerebellar Purkinje neurons. A recent study showed that a 14-mer fragment of a mouse beta4 subunit, beta4(154-167), acts as an intracellular open-channel blocker and elicits resurgent currents in Purkinje neurons (Grieco, T.M., J.D. Malhotra, C. Chen, L.L. Isom, and I.M. Raman. 2005. Neuron. 45:233-244). To explore these phenotypes in vitro, we characterized beta4(154-167) actions in inactivation-deficient cardiac hNav1.5 Na(+) channels expressed in human embryonic kidney 293t cells. Intracellular beta4(154-167) from 25-250 microM elicited a conspicuous time-dependent block of inactivation-deficient Na(+) currents at 50 mV in a concentration-dependent manner. On and off rates for beta4(154-167) binding were estimated at 10.1 microM(-1)s(-1) and 49.1 s(-1), respectively. Upon repolarization, large tail currents emerged with a slight delay at -140 mV, probably as a result of the rapid unblocking of beta4(154-167). Near the activation threshold (approximately -70 mV), resurgent tail currents were robust and long lasting. Likewise, beta4(154-167) induces resurgent currents in wild-type hNav1.5 Na(+) channels, although to a lesser extent. The inactivation peptide acetyl-KIFMK-amide not only restored the fast inactivation phenotype in hNav1.5 inactivation-deficient Na(+) channels but also elicited robust resurgent currents. When modified by batrachotoxin (BTX), wild-type hNav1.5 Na(+) channels opened persistently but became resistant to beta4(154-167) and acetyl-KIFMK-amide block. Finally, a lysine substitution of a phenylalanine residue at D4S6, F1760, which forms a part of receptors for local anesthetics and BTX, rendered cardiac Na(+) channels resistant to beta4(154-167). Together, our in vitro studies identify a putative S6-binding site for beta4(154-167) within the inner cavity of hNav1.5 Na(+) channels. Such an S6 receptor readily explains (1) why beta4(154-167) gains access to its receptor as an open-channel blocker, (2), why bound beta4(154-167) briefly prevents the activation gate from closing by a "foot-in-the-door" mechanism during deactivation, (3) why BTX inhibits beta4(154-167) binding by physical exclusion, and (4) why a lysine substitution of residue F1760 eliminates beta4(154-167) binding.

Ephedrine blocks rat sciatic nerve in vivo and sodium channels in vitro.

BACKGROUND: The sympathomimetic drug ephedrine has been used intrathecally as the sole local anesthetic for labor and delivery. Because ephedrine may be a useful adjuvant to local anesthetics, the authors investigated the local anesthetic properties of ephedrine in a rat sciatic nerve block model and the underlying mechanism in cultured cells stably expressing Na channels. METHODS: After approval of the animal protocol, the sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs, 0.2 ml ephedrine at 0.25, 1, 2.5, or 5% and/or bupivacaine at 0.125% was injected, and the wound was closed. Motor and sensory/nociceptive functions were evaluated by the force achieved by pushing against a balance and the reaction to pinch, respectively. The whole cell configuration of the patch clamp technique was used to record Na currents from human embryonal kidney cells stably transfected with Nav1.4 channels. RESULTS: The nociception blockade was significantly longer than the motor blockade at test doses of 2.5 and 5% of ephedrine, or when 1% ephedrine was combined with 0.125% bupivacaine (analysis of variance with repeated measures, P < 0.001, n = 8/group). In vitro, the 50% inhibitory concentrations of ephedrine at -150 and -60 mV were 1,043 +/- 70 and 473 +/- 13 mum, respectively. High-frequency stimulation revealed a use-dependent block of 18%, similar to most local anesthetics. CONCLUSIONS: Because ephedrine's properties are at least partly due to Na channel blockade, detailed histopathologic investigations are justified to determine the potential of ephedrine as an adjuvant to clinically used local anesthetics.