Patients admitted to the intensive care unit (ICU) may require muscle relaxation with neuromuscular blocking agents (NMBAs) for various indications. Due to the complex pharmacokinetic and pharmacodynamic parameters of available agents for the neuromuscular blockade of critically ill adults, continuous infusions and frequent titration are often necessary to achieve therapeutic goals. In determining the need for titration, therapeutic goals are assessed using parameters such as synchrony with ventilator support and train of four (TOF) assessments ⁽¹⁾.

The selection of appropriate patients and appropriate duration is especially important since these agents have high risks, such as intensive care unit-acquired weakness (ICU-AW), elongated mechanical ventilation duration, awareness during paralysis, deep vein thrombosis, corneal abrasions and anaphylaxis, especially during long-term use.

1. Facilitation of mechanical ventilation

2. Severe acute respiratory distress syndrome (ARDS)

3. Unconventional ventilatory modes (pressure control, inverse I:E ratio, prone ventilation)

4. Significant patient-ventilatory asynchrony

5. Life threatening status asthmaticus with profound hypoxemia, respiratory acidosis, or hemodynamic compromise

6. To control increased intracranial pressure

7. Supportive therapy for muscle spasms, tetanus, or neuroleptic malignant syndrome

8. Prevention of shivering with therapeutic hypothermia protocols

9. Increased intra-abdominal pressure

10. Facilitation of procedures or diagnostic studies such as magnetic resonance imaging (MRI) or computed tomography (CT)

11. Facilitation of safe intra or inter hospital transfer.

Prior to the implementation of NMBA, all patients should be assessed for the following conditions and proactively treated to prevent increased morbidity:

a) Venous thromboembolism (VTE) prophylaxis: VTE prophylaxis should be administered with either low molecular weight heparin or unfractionated heparin if no contraindications exist. Patients are at increased risk for deep venous thrombosis and pulmonary embolism due to immobility.

b) Scheduled eye lubrication: To prevent keratitis, corneal abrasions, soft tissue or nerve injury and skin breakdown, artificial tears ophthalmic ointment e.g., carbomer gel should be applied as a thin strip to each eye every 4 hours.

c) Taping eyes shut or using a patch to cover eyes may also be considered in addition to applying eye lubrication.

d) All patients should receive careful passive range of motion.

e) All patients should have pressure points carefully padded and regularly assessed.

Smooth muscle is unaffected by NMBAs so enteral feeding remains an option for nutritional support in critically ill patients receiving NMBAs.

Rocuronium bromide is an amino-steroid neuromuscular blocking drug with an intermediate duration of action. It exerts an effect within 2 minutes and has the most rapid onset of any of the non-depolarising neuromuscular blocking drugs. It is reported to have minimal cardiovascular effects; high doses produce mild vagolytic activity.

Atracurium besilate is a benzylisoquinolinium neuromuscular blocking drug with an intermediate duration of action. It undergoes non-enzymatic metabolism, which is independent of liver and kidney function, thus allowing its use in patients with hepatic or renal impairment. Cardiovascular effects are associated with significant histamine release; histamine release can be minimised by administering slowly or in divided doses over at least 1 minute.

Cisatracurium is an isomer of atracurium. It is more potent, has a slightly longer duration of action than atracurium besilate, and provides greater cardiovascular stability because cisatracurium lacks histamine-releasing effects.

To avoid excessive dosage in obese patients, dose should be calculated with ideal body weight.

All patients receiving NMBAs should be monitored to avoid awareness during paralysis.

There are several scales used but Richmond Agitation and Sedation Score (RASS) is used within the Trust ICUs.

The goal during muscle paralysis is RASS of –5.

Other techniques based on processed EEG monitoring like BIS or entropy can be used as adjuncts but not solely⁽²⁾.

Guidance from NAP5 2014⁽⁶⁾, NICE 2012⁽⁷⁾, RCoA⁽⁸⁾ and AAGBI⁽⁹⁾ recommend processed EEG monitoring for all paralysed patients receiving intravenous anaesthesia. In the absence of ICU specific guidance, its use is at clinician’s discretion, but they should note the recommendations from NAP5, NICE, the RCoA and AAGBI above.

TOF monitoring should be utilised for all patients receiving continuous infusion of NMBA⁽¹⁾. TOF is a method of measuring magnitude of neuromuscular blockade, based upon the ratio of the amplitude of the fourth evoked mechanical response to the first one, when 4 electrical currents are applied for 2 seconds to a peripheral motor nerve.

The correct placing of the electrodes is shown in Appendix ⁽¹⁰⁾.

1. Discuss with ICU Consultant, check no contraindications, and confirm the choice of drug.

2. Provide the patient with adequate ventilation.

3. Ensure adequate pain control and sedation are achieved prior to neuromuscular blockade, evidenced by a RASS of -5.

4. Test baseline TOF response. Start with low voltage of 10-20 mA and increase it slowly in increments of 10mA until four twitches are observed.

5. Administer the bolus dose of the chosen NMBA and start the infusion.

6. Check TOF every 30 minutes until infusion rate has been stable for 2 tests and then check routinely every 4 hours.

   1. If more than 2 twitches seen or felt – increase the infusion by 10% or discuss with ICU Doctor if bolus dose needed. Repeat TOF in 30 minutes.

   2. If less than 2 twitches seen or felt – decrease the infusion by 10% and repeat TOF in 30 minutes.

7. Discuss daily breaks in NMBA infusion with ICU Consultant.

8. Daily reassessment of the need for ongoing paralysis and termination of the blockade should be performed at the earliest possible time.

1. Bouju, P., Tadié, JM., Barbarot, N. et al. Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study. Ann Intensive Care 2017: 7 (1): 10. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247382/ (Accessed 5 Nov 2024)

2. Whitehouse, T., Snelson, C. and Grounds, M.; Intensive Care Society Review of Best Practice for Analgesia and Sedation in the Critical Care; ICS 2014. Available at: https://www.wyccn.org/uploads/6/5/1/9/65199375/sedation_for_patients_in_icu_2014.pdf (Accessed 5 Nov 2024)

3. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Available at: http://www.medicinescomplete.com (Accessed 5 Nov 2024)

4. Gursoy, S., Bagsivan, I., Durmus, N., Kaygusuz, K., Kol, I., Duger, C., Yildirim, S., Mimaroglu, C., ;Investigation of the cardiac effects of pancuronium, rocuronium, vecuronium, and mivacurium on the isolated rat atrium Current therapeutic research, clinical and experimental; Oct 2011: 72 (5): 195-203 Available at: https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0011393X11001159?returnurl=null&referrer=null (Accessed 5 Nov 2024)

5. Pandit J., Cook T. Royal College of Anaesthetists (2014) Accidental Awareness during General Anaesthesia in the United Kingdom and Ireland: Report and findings. Available at: https://www.nationalauditprojects.org.uk/downloads/NAP5%20full%20report.pdf (Accessed 5 Nov 2024)

6. National Institute for Health and Care Excellence (2012) Depth of anaesthesia monitors – Bispectral Index (BIS), E-Entropy and Narcotrend-Compact M Available at: https://www.nice.org.uk/guidance/dg6/resources/depth-of-anaesthesia-monitors-bispectral-index-bis-eentropy-and-narcotrendcompact-m-pdf-29275661509 (Accessed 5 Nov 2024)

7. Patil V., Joachim S., Kumar M., Connor D. and Banerjee A. Royal College of Anaesthetists (2019) Chapter 3: Guidelines for the Provision of Anaesthesia Services for Intraoperative Care 2019 Available at: GPAS-2019-03-INTRAOP.pdf (Accessed 5 Nov 2024)

8. Klein, A.A., Meek, T., Allcock, E., Cook, T., Mincher, N., Morris, C., Nimmo, A.F., Pandit, J.J., Pawa, A., Rodney, G., Sheraton, T., Young, P., ; Association of Anaesthetists (2021) Guidelines: Recommendations for standards of monitoring during anaesthesia and recovery 2021 Available at: https://anaesthetists.org/Home/Resources-publications/Guidelines/Recommendations-for-standards-of-monitoring-during-anaesthesia-and-recovery-2021 (Accessed 5 Nov 2024)

9. Naguib, M., Brull, S.J., Johnson, K.B.; Conceptual and technical insights into the basis of neuromuscular monitoring. Anaesthesia 2017; 72 (Suppl 1); 16-37. Available at: https://doi.org/10.1111/anae.13738 (Accessed 5 Nov 2024)

Figure 1

Representation of correct placement of the stimulating electrodes for ulnar nerve stimulation. Note that the black (negative) electrode is distal to the proximal, red (positive) electrode.

Figure 2

Subjective (tactile) evaluation of neuromuscular responses at the adductor pollicis (thumb) muscle in response to ulnar nerve stimulation. Note the negative (black) electrode is placed distally.

Figure 3

(a) (b)

Suggested placement of stimulating electrodes for monitoring of the eye (orbicularis oculi, corrugator supercilii) muscles. Given the course of the facial nerve, note that the positive (red) electrode is always proximal and the negative (black) electrode always distal.

Figure 4

Subjective (tactile) evaluation of neuromuscular responses at the orbicularis oculi (eye) muscle in response to facial nerve stimulation. Note the negative (black) electrode is placed distally.

This guideline has been registered with the Trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague or expert. Caution is advised when using guidelines after the review date.
This guideline is for use in Frimley Health NHS Foundation Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

Version History

Related Documents

None