Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient

"OBJECTIVE: To update the 2002 version of ""Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient."" DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. RESULTS: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death."

Lateral migration of a capsule in a parabolic flow.

Red blood cells migrate to the center of the blood vessel in a process called axial migration, while other blood cells, such as white blood cells and platelets, are disproportionately found near the blood vessel wall. However, much is still unknown concerning the lateral migration of cells in the blood; the specific effect of hydrodynamic factors such as a wall or a shear gradient is still unclear. In this study, we investigate the lateral migration of a capsule using the boundary integral method, in order to compute exactly an infinite computational domain for an unbounded parabolic flow and a semi-infinite computational domain for a near-wall parabolic flow in the limit of Stokes flow. We show that the capsule lift velocity in an unbounded parabolic flow is linear with respect to the shear gradient, while the lift velocity in a near-wall parabolic flow is dependent on the distance to the wall. Then, using these relations, we give an estimation of the relative effect of the shear gradient as a function of channel width and distance between the capsule and the wall. This estimation can be used to determine cases in which the effect of the shear gradient or wall can be neglected; for example, the formation of the cell-free layer in blood vessels is determined to be unaffected by the magnitude of the shear gradient.

Lateral migration of a spherical capsule near a plane wall in Stokes flow.

Lateral migration is the motion of a particle perpendicular to the direction of the surrounding flow. One of the factors leading to the lateral migration of a deformable particle in Stokes flow is the presence of a nearby wall. We numerically investigate the lateral migration of a capsule in a near-wall simple shear flow using a boundary integral method coupled with a finite element method. We find that asymmetrical deformation of the capsule induced by the wall is correlated with a reduction in the lift velocity relative to the lift velocity predicted by a far-field analytical solution. A combination of this asymmetrical deformation, which decreases the lift velocity, and an increase in the value of the capsule stresslet near the wall, which works to increase the lift velocity, leads to a migration velocity that is nearly independent of capillary number and membrane constitutive law at large deformation near the wall.

Characteristics of foot structure and footwear associated with hallux valgus: a systematic review.

OBJECTIVE: Factors associated with the development of hallux valgus (HV) are multifactorial and remain unclear. The objective of this systematic review and meta-analysis was to investigate characteristics of foot structure and footwear associated with HV. DESIGN: Electronic databases (Medline, Embase, and CINAHL) were searched to December 2010. Cross-sectional studies with a valid definition of HV and a non-HV comparison group were included. Two independent investigators quality rated all included papers. Effect sizes and 95% confidence intervals (CIs) were calculated (standardized mean differences (SMDs) for continuous data and risk ratios (RRs) for dichotomous data). Where studies were homogeneous, pooling of SMDs was conducted using random effects models. RESULTS: A total of 37 papers (34 unique studies) were quality rated. After exclusion of studies without reported measurement reliability for associated factors, data were extracted and analysed from 16 studies reporting results for 45 different factors. Significant factors included: greater first intermetatarsal angle (pooled SMD = 1.5, CI: 0.88-2.1), longer first metatarsal (pooled SMD = 1.0, CI: 0.48-1.6), round first metatarsal head (RR: 3.1-5.4), and lateral sesamoid displacement (RR: 5.1-5.5). Results for clinical factors (e.g., first ray mobility, pes planus, footwear) were less conclusive regarding their association with HV. CONCLUSIONS: Although conclusions regarding causality cannot be made from cross-sectional studies, this systematic review highlights important factors to monitor in HV assessment and management. Further studies with rigorous methodology are warranted to investigate clinical factors associated with HV.

hCASK and hDlg associate in epithelia, and their src homology 3 and guanylate kinase domains participate in both intramolecular and intermolecular interactions.

Membrane-associated guanylate kinase (MAGUK) proteins act as molecular scaffolds organizing multiprotein complexes at specialized regions of the plasma membrane. All MAGUKs contain a Src homology 3 (SH3) domain and a region homologous to yeast guanylate kinase (GUK). We showed previously that one MAGUK protein, human CASK (hCASK), is widely expressed and associated with epithelial basolateral plasma membranes. We now report that hCASK binds another MAGUK, human discs large (hDlg). Immunofluorescence microscopy demonstrates that hCASK and hDlg colocalize at basolateral membranes of epithelial cells in small and large intestine. These proteins co-precipitate from lysates of an intestinal cell line, Caco-2. The GUK domain of hCASK binds the SH3 domain of hDlg in both yeast two-hybrid and fusion protein binding assays, and it is required for interaction with hDlg in transfected HEK293 cells. In addition, the SH3 and GUK domains of each protein participate in intramolecular binding that in vitro predominates over intermolecular binding. The SH3 and GUK domains of human p55 display the same interactions in yeast two-hybrid assays as those of hCASK. Not all SH3-GUK interactions among these MAGUKs are permissible, however, implying specificity to SH3-GUK interactions in vivo. These results suggest MAGUK scaffold assembly may be regulated through effects on intramolecular SH3-GUK binding.

Ksp-cadherin gene promoter. I. Characterization and renal epithelial cell-specific activity.

Kidney-specific cadherin (Ksp-cadherin, cadherin 16) is a novel, kidney-specific member of the cadherin superfamily that is expressed exclusively in the basolateral membrane of renal tubular epithelial cells. To characterize the Ksp-cadherin gene promoter, a lambda bacteriophage clone containing 3.7 kb of the proximal 5' flanking region of the mouse Ksp-cadherin gene was isolated. The transcription initiation site was mapped by RNase protection assays and 5' rapid amplification of cDNA ends, and a 709-bp intron was identified within the 5' untranslated region. The proximal 5' flanking region was "TATA-less" but contained other consensus promoter elements including an initiator (Inr), GC boxes, and a CAAT box. Potential binding sites were identified for transcription factors that are involved in tissue-specific gene expression including activator protein-2 (AP-2), hepatocyte nuclear factor-3 (HNF-3), basic helix-loop-helix (bHLH) proteins, CCAAT/enhancer-binding protein (C/EBP), and GATA factors. Transfection of luciferase reporter plasmids containing 2.6 kb of the 5' flanking region markedly increased luciferase activity in renal epithelial cells (MDCK and mIMCD-3) but not in mesenchymal cells (NIH 3T3 and MMR1). Deletion analysis identified an 82-bp region from -31 to -113 that was essential for promoter activity in transfected renal epithelial cells. Electrophoretic mobility-shift assays showed that mIMCD-3 cells contain nuclear proteins that bind to this region of the promoter. Mutational analysis showed that sequences within the HNF-3 consensus site and CAAT box were involved in protein binding and promoter activity. We conclude that the proximal 5' flanking region of the mouse Ksp-cadherin gene contains an orientation-dependent promoter that is kidney epithelial cell specific. The region of the promoter from -113 to -31 is required for transcriptional activity and contains binding sites for nuclear proteins that are specifically expressed in renal epithelial cells.

Developing a computer-assisted health knowledge quiz for preschool children.

The project evaluated the reliability of a computer-assisted health education knowledge quiz, a multiple-choice picture identification assessment tool for nutrition and health-related knowledge in preschool age children. Pearson's product moment correlation coefficients were computed to assess overall and componential stability between test/retest scores of 51 children (mean age 3.6 years) enrolled in a Head Start preschool center. Cronbach alpha coefficients were calculated to determine the internal consistency of the subscales. Overall reliability for the computer-assisted quiz was high at .82 (p < .01). For individual subscales, test/retest correlations were highest for Nutrition, Safety, and Environment (r = .56 to .81) and lower but still significant for Dental, Smoking, and Fitness (r = .37 to .48). Results suggest a computer-assisted knowledge quiz can provide a reliable tool to assess health education knowledge in young children. In addition, the computer-assisted test format is highly acceptable to preschool children and enables researchers to administer a more extensive test to young children with brief attention spans in a manner that engages their full cooperation and effort. In this respect it offers several advantages over traditional paper-and-pencil formats.

Comparison of the MB/BacT system with a revised antibiotic supplement kit to the BACTEC 460 system for detection of mycobacteria in clinical specimens.

The MB/BacT system (MB/BacT) with a revised antibiotic supplement kit was compared with the BACTEC 460 system (BACTEC 460) in a test of 488 specimens submitted for mycobacterial culture from 302 patients. Twenty-four Mycobacterium tuberculosis isolates were detected by the BACTEC 460 versus 23 isolates by the MB/BacT. Mean time until detection of M. tuberculosis isolates identified by both systems was 11.9 days for the BACTEC 460 versus 13.7 days for the MB/BacT (P = 0.046). M. avium complex was detected in 12 specimens by the MB/BacT versus 10 specimens by the BACTEC 460. Only 8 of 14 (57%) M. avium isolates were detected by both systems, with a mean time until detection of 10.1 days for the BACTEC 460 and 14.2 days for the MB/BacT (P = 0.009). The BACTEC 460 and the MB/BacT detected M. gordonae in four specimens, but only a single specimen was positive by both systems. One M. fortuitum isolate and one of five M. kansasii isolates were recovered only by the BACTEC 460. The bacterial overgrowth rate was 7.0% for the MB/BacT versus 4.1% for the BACTEC 460. We found the MB/BacT to be comparable to the BACTEC 460 for mycobacterial detection. Even though time until detection with the MB/BacT was slightly longer (1.8 days longer for M. tuberculosis and 4.1 days for M. avium [mean values]) and the bacterial overgrowth rate was somewhat higher, the decreased labor, the availability of a computerized data management system, and the noninvasive, nonradiometric aspects of the MB/BacT offset these relative disadvantages and make it an acceptable alternative for use in the diagnostic laboratory.

Comparative in vitro activities of four new fluoroquinolones against Streptococcus pneumoniae determined by Etest.

Clinafloxacin, levofloxacin, sparfloxacin and trovafloxacin were tested by Etest against 188 Streptococcus pneumoniae isolates. Clinafloxacin and trovafloxacin were 2-4-fold more potent than sparfloxacin and 8-fold more than levofloxacin. Two isolates, both serotype 6, with high-level quinolone resistance (> or = 8 micrograms/ml) were detected. The Etest is a practical means for determining S. pneumoniae susceptibilities to new fluoroquinolones.

Psychological stress and the passage of a standard meal through the stomach and small intestine in man.

Gastric emptying half-time and mouth to caecum transit time of a solid meal were measured in eight normal volunteers, once during a period of psychological stress and again during a period of relative calm. No consistent or significant effect on gastric emptying was observed, but mouth to caecum transit times were faster in all subjects and this difference was highly significant (p<0.01).