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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.

Intensivists use neuromuscular blocking agents for a variety of clinical conditions, including for emergency intubation, acute respiratory distress syndrome, status asthmaticus, elevated intracranial pressure, elevated intra-abdominal pressure, and therapeutic hypothermia after ventricular fibrillation-associated cardiac arrest. The continued creation and use of evidence-based guidelines and protocols could ensure that neuromuscular blocking agents are used and monitored appropriately. A collaborative multidisciplinary approach coupled with constant review of the pharmacology, dosing, drug interactions, and monitoring techniques may reduce the adverse events associated with the use of neuromuscular blocking agents.

Objectives: To determine the clinical effects of intravenous terbutaline at >0.4 microg/kg/min in children with status asthmaticus; to describe the clinical findings associated with such therapy, including creatinine phosphokinase-myocardial band isoenzyme (CPK-MB) concentrations, electrocardiographic alterations, and decreased diastolic blood pressure (DBP) with terbutaline usage; and to assess the requirement for epinephrine to counteract the decrease in diastolic blood pressure., Design: A retrospective review of children admitted with status asthmaticus who failed emergency room therapy and required intravenous terbutaline., Setting: San Diego Children's Hospital Pediatric Intensive Care Unit., Patients: Eighteen children with status asthmaticus, based on clinical and laboratory criteria, between September 1994 and July 1996., Interventions: Epinephrine was added for below-normal decreases in diastolic blood pressure., Measurements and Main Results: Continuous monitoring for arrhythmias, ST-segment changes, and DBP values during variations in the dose of intravenous terbutaline, with or without epinephrine. CPK-MB concentrations were determined in 15 of 18 patients., Conclusions: Intravenous terbutaline was well tolerated in asthmatic children for < or =305 continuous hours and at varying doses up to a maximum of 10 microg/kg/min. There was no relationship between the magnitude of CPK-MB concentrations and the terbutaline or epinephrine doses used. Arrhythmias were rare and not related to either terbutaline or epinephrine doses. However, ST-segment depression did occur in two patients requiring high-dose epinephrine. Terbutaline significantly lowered DBP when used between 0.4 and 1.0 microg/kg/min, which required epinephrine to be initiated. Epinephrine was not required at terbutaline doses of >2 microg/kg/min. There was no mortality.

Objectives: a) to determine if continuous nebulization of albuterol is more effective than intermittent nebulization in the treatment of children with status asthmaticus and impending respiratory failure; b) to determine the effect of continuous nebulization and intermittent nebulization on duration of hospital stay and bedside respiratory therapy care., Design: Prospective, randomized study., Setting: A pediatric intensive care unit (ICU) in a university children's hospital., Patients: Seventeen pediatric asthmatic patients with severe status asthmaticus, with impending respiratory failure (Woods asthma score > or = 5), and without evidence of cardiac or other preexisting lung disease were admitted to the pediatric ICU. The patients were randomized to receive continuous nebulization (n = 9) or intermittent nebulization (n = 8) of albuterol., Interventions: The asthmatic patients were randomized into two groups. The continuous group received 0.3 mg/kg/hr of albuterol by continuous nebulization; the intermittent group received 0.3 mg/kg of albuterol over 20 mins every hour. All patients received aerosol therapy through the same delivery system., Measurements: Responses to therapy were evaluated by following asthma score, arterial blood gas values, hemodynamics, FIO2, and arterial oxygen saturation initially and at 30 mins, 1 hr, 2 hrs, 4 hrs, then every 4 hrs for a 24-hr time period. Patients were determined to no longer be in impending respiratory failure when their asthma score was < 5 for four consecutive hours. Electrocardiograms, serum electrolyte values, and creatine phosphokinase total and MB fraction values were obtained before and after treatment. Hospital stay and respiratory therapy time, in relative value units (one relative value unit = 10 mins) were analyzed from data collected from therapist bedside flow sheets., Results: The patient characteristics (demographics, hemodynamics, arterial blood gas values, asthma severity, corticosteroid use, theophylline, and beta 2-adrenergic receptor agonist administration) before entry into the study did not differ between groups. Patients in the continuous group improved more rapidly and were out of impending respiratory failure sooner than patients in the intermittent group (continuous group = 12 (median) hrs (range 4 to 24) vs. intermittent group = 18 (median) hrs (range 12 to 24; p = .03). Bedside respiratory therapy time evaluated by relative value units was less for patients who received continuous nebulization of albuterol (continuous group = 14 (median) relative value units (range 6 to 26) vs. intermittent group = 33 (median) relative value units (range 25 to 49; p = .001). Hospital stay was shorter for patients who received continuous nebulization of albuterol (continuous group = 80 [median] hrs [range 51 to 173] vs. intermittent group = 147 [median] hrs [range 95 to 256]; p = .043). Hemodynamics, serum potassium, and creatine phosphokinase concentrations did not differ before and after the study in either group., Conclusions: In children with impending respiratory failure due to status asthmaticus, continuous nebulization of albuterol is safe and results in more rapid clinical improvement than intermittent nebulization. Respiratory therapy required at the bedside and duration of hospital stay were substantially less for patients receiving continuous nebulization of albuterol, which suggests that continuous nebulization of albuterol is more cost effective than intermittent nebulization.

The management of status asthmaticus using a continuous iv infusion of salbutamol was studied in 14 children with a total of 16 episodes of respiratory failure, unresponsive to conventional bronchodilator therapy. The mean PaCO2 at the start of the infusion was 60 +/- 6 torr. A loading dose of 1 microgram/kg X min body weight was given over 10 min, followed by an infusion of 0.2 microgram/kg X min which was increased in 0.1-microgram/kg steps according to response. The maximum dose was 4 microgram/kg X min. On 11 (69%) occasions a sustained reduction in PaCO2 was achieved within 4 h of starting the infusion. In 5 (11%) instances no reduction in PaCO2 was seen and mechanical ventilation was instituted because of increasing respiratory distress and CO2 retention. Mean heart rate during the infusion increased from 161 to 183 beat/min. Comparison with previous data from 30 pediatric patients (40 infusions) receiving iv isoproterenol showed less effect on heart rate and a more sustained fall in PaCO2 without the recurrence of bronchospasm. We found salbutamol to be a safe and effective bronchodilator capable of reversing severe bronchospasm in most children who would otherwise require mechanical ventilation. Its greater specificity for beta 2-receptors may make it preferable to isoproterenol.