Neuromuscular Blocker In Ards

Neuromuscular Blockers in
Early Acute Respiratory
Distress Syndrome

 Provide the background info of the journal
 Provide a brief overview of ARDS and its management
 Discuss the overview of a previous clinical trial
 Explain the methodology of the study
 Display the assessed endpoints and the results of the
study
 Discuss author’s strengths and weakness of the study
 Provide my critique of the study
 Assess the appropriateness of use in clinical practice

 New England Journal of
Medicine
 English language peer
reviewed medical journal,
published by the
Massachusetts Medical
Society
 Founded in 1812- one of the
oldest medical journal in the
world
 Publishes editorials, primary
research article, review
articles, and case reports

 Life threatening condition
 The lung is damaged to a point where it can no
longer function properly in exchange of airlow
level of oxygen in the blood
 Fluids starts to accumulate in the air sacs
 Makes the lung heavy and stiff decreasing its ability
to expand

http://emedicine.medscape.com/article/165139-overview

 Any sort of swelling or injury to the lung
▪ Aspiration
▪ Chemical Inhalation
▪ Pneumonia
▪ Septic Shock
▪ Trauma

 Shortness of breath
 Labored, rapid breathing
 Hypotension
 Cold extremities

 Ausculating the chest with a stethoscope
 Abnormal lung sounds
▪ Crackles-accumulation of fluid in the lungs
 In order to help diagnose ARDS, the following
tests are usually done
▪ CBC-no expected lab abnormalities
▪ Sputum Cultures
▪ Chest X-Ray
▪ ECG or Swan-Ganz catheterization rule out CHF
▪ Arterial blood gas-PaO2/FiO2 ratio of ≤ 200

PROGNOSIS
 1/3 of patient expires
 Patients that do
recover usually have
memory loss or other
problems due to the
brain damage
COMPLICATIONS
 Lung damage
 Organ system failure
 Ventilator-associated
pneumonia

 Patient’s are admitted into
the ICU
 Goal:
 Treat the underlying cause
▪ ABX if infection
▪ reduce the inflammation
▪ remove the fluid out of the
lungs
 Provide breathing support
 Patients are intubated and
put on a ventilator
 Deliver high dose of oxygen via CPAP http://www.aic.cuhk.edu.hk/web8/Hi%20res/Intubation.jpg

 Indication
 Adjunct to general anesthesia
 Facilitate intubation and procedures, and mechanical
ventilation
 Manage increased intracranial pressure
 Treat muscle spasms
▪ Hypothermia after cardiac arrest
 Decrease oxygen demand

 Pharmacology
 Inhibits the cholinergic
receptors on the motor
end-plate to antagonize
the action of acetylcholine,
resulting in the blockage of
neural transmission
 Can be antagonized by
Neostigmine (Prostigmin)
▪ 0.5mg – 2 mg IV PRN-
slow IV push
http://www.ispub.com/ispub/ijos/volume_7_number_2_7/orthopaedic_surgery_implications_of_a_nov
el_encapsulation_process_that_improves_neuromuscular_blockade_and_reversal/nmb-fig3.jpg

pancuronium vecuronium rocuronium
- An aminosteroid
- Duration of paralysis- 90-
100 minutes
- Recovery-120 to 180
minutes
- Elimination
- Renal-45-75%
- Bile-10 to 15%
- Renal failure- increase
duration of the drug
- Common ADR
- elevated heart rate
- muscle weakness
- elevated BP
-An aminosteroid
- Duration of paralysis-35-
45 minutes
-Takes about 45-60
minutes to recover
- Elimination
-Renal- 50%
-Bile-35-50%
-Renal failure- Increased
duration of the drug
-The drug has active
metabolites
- Common ADR
- muscle weakness
- elevated heart rate
- respiratory depression
- An aminosteroid
- Duration of paralysis- 30
minutes
- Recovery- 20-30 minutes
- Elimination
-Renal- 33%
- BiliaryTract- 75%
-The drug has no active
metabolites
- Renal failure- minimal
effect on the duration of
the drug.
-CommonADR
-Transient Hypotension
-Muscle weakness

 Dosing
 Adults
▪ 150-200 mcg/kg IV x 1
 Pediatrics
▪ 0.03mg/kg IV
 Warnings/precautions
 May have profound effects in
patients with neuromuscular
disease such as myasthenia
gravis
▪ Use a dose no more than
0.02mg/kg http://www.ismp.org/images/PACKAGING/NIMBEX.gif

 Pharmacokinetics
 80% of drug is metabolized by the liver
 95% excreted in the urine; 4% excreted in the feces
 Elimination half life: 22-29 minutes
 Renal Failure- No dose adjustment required

 Adverse Reactions (<1%)
 Bradycardia
 Hypotension
 Flushing
 Bronchospasm

 Drug Interactions
 Aminoglycosides
▪ Combo may potentiate, prolong neuromuscular blockade
▪ avoid combo or monitor closely
 Quinidine
▪ Potentiate neuromuscular blockade by synergistic effect
▪ use alternative or avoid quinidine 24h after neuromuscular blocker use
 Inhaled anesthetics ( enflurane, isoflurane,
desflurane, sevoflurane)
▪ Potentiate and prolong neuromuscular blockade by providing an
additive/synergistic effects

 Kidney or Liver Disease- Cisatracurium
 Monitor Clinically-Train of four
 Four electrical pulses are transmitted to the ulnar
nerve
▪ If four pulses- no blockade
▪ Goal= 1-2 pulse

 Grannier M, Roch A, Forel JM, et al. Effects of
neuromuscular blocking agents on gas exchange in
patients presenting with acute respiratory distress
syndrome
 To evaluate the effects of a 48hr NMBA infusion on gas
exchange over 120-hr time period in patients with ARDS
 Design: Multicenter, Open label-prospective, controlled,
and randomized trial
 N=56 pt’s with ARDS
 Intervention: ConventionalTherapy or Conventional
therapy PLUS cisatracurium

 Primary endpoint
 Improvement in oxygenation within w/in 120 hours after
randomization
 Result: Administering NMBA up to 48 hours in patients with
ARDS, improves oxygenation and a decrease trend toward
mortality in the ICU compared to patients who did not
receive NMBA’s
 Limitation
 Was not designed or powered to evaluate mortality.
 Further study on benefits and risk of NMBA’s in ARDS patients
receiving ventilation is required

 To determine whether treatment with cisatrocurium for
a short period of time would improve clinical outcomes
in the course of severe ARDS

 Patients who received endotracheal mechanical
ventilation for acute hypoxemic respiratory
failure PLUS the presence of the following for up
to 48 hours:
 PaO2:FiO2 less than 150
 Bilateral pulmonary infiltrates that were consistent
with edema
 Absence of clinical evidence of left atrial hypertension
▪ Pulmonary-capillary wedge pressure of less than 18 mmHg

 Age < 18 years
 Lack of consent
 Continuous infusion of
NMBA’s at enrollment
 Known pregnancy
 Enrollment in another trial
within the previous 30 days
 Increased intracranial
pressure
 Severe chronic respiratory
disease requiring long-term
oxygen therapy or mechanical
ventilation at home
 Actual body weight> 1 kg/cm
of height
 Severe chronic liver disease
 Bone marrow transplantation
or chemotherapy-induced
neutropenia
 Pneumothorax
 Expected duration of
mechanical ventilation of less
than 48 hours
 Decision to withhold life-
sustaining treatment

 Study Design
 Multicenter, randomized, placebo-controlled, double-
blind clinical trial
 Monitored by an independent data and safety
monitoring board
 Consolidated Standards for the Reporting ofTrials
(CONSORT) guidelines
▪ Performed randomization and blinding regarding of the
study group

 March 2006 – March 2008; 340 patients in 20
ICU’s in France
 1326 patients were assessed for eligibility; and
986 patients met the exclusion criteria.
 Written consent were obtained from patients or
from the patients proxies

 Primary
 Proportion of patients who died before hospital discharge and within 90 days
after enrollment
 Secondary
 28-day mortality
 Numbers of days outside the ICU between day 1 and 28 and between day 1 and
90
 Numbers of ventilator-free days between day 1 and day 28 and between day 1
and day 90.
▪ If the patient died before day 28 or before day 90, then the number of
ventilator free days were considered to be zero
 Numbers of days without organ or system failure between day 1 and day 28
 Rate of ICU-acquired paresis
 Medical Research Council (MRC) scores on day 28 to assess the three muscle
groups in each arm and leg, between 0 (paralysis) to 5 (normal strength)
 The time of ICU discharge

 cisatracurium besylate vs. placebo via IV infusion
 Patients were sedated and then given a 3mL(15mg)
rapid intravenous infusion of cisatracurium or placebo
were administered, followed by a 37.5 mg per hour for
48 hours
 Patients were put on a ventilator that was set to deliver
a tidal volume of 6-8 mL/Kg of O2
 If the end-inspiratory plateau pressure > 32 cm of water
for at least 10 minutes open-label, rapid, intravenous
injection of 20 mg of cisatracurium

 If end-inspiratory plateau pressure decreased by less than 2cm of
water second injection of 20mg cisatracurium administered
 If the end-inspiratory plateau pressure did not decrease or
decreased by less than 2 cm of water, then no administration of
cisatrocurium were given for the next 24 hours
 Patients were monitored every day for up to 28 days for signs of
non pulmonary organ failure:
 Circulatory failure= SBP of 90 mmHg or less, need for vasopressor
 Coagulation failure= Platelet count of 80,000 or less per cubic mL.
 Hepatic failure= Serum bilirubin of 2 mg/dL or higher
 Renal Failure= SCr of 2 mg/dL or higher

 Sample size were calculated based on the
authors previous study which used the same
inclusion criteria and the ALIVE study
 Estimated that a 340 patients would needed to
be enrolled to detect a 15% absolute reduction in
the 90 day mortality in the cisatracurium group
compared to the placebo
 P= 80% and a 2 sided alpha value of 0.05

 90 day mortality in
the cisatrocurium
group Vs. placebo
 31.6% (95% CI, 25.2 to
38.8) vs. 40.7% (95% CI,
33.5-48.4) (p= 0.08)

 Treating patients with NMBA’s for 48 hours early
in the course of therapy with low-tidal-volume
ventilation
 improves the adjusted 90 day survival rate
 increases the number of days off of the ventilator
 Increases days spent outside the ICU
 decreases the occurrences of any sort of barotraumas in the
first 90 days
 Did not improve the overall 90-day mortality
significantly

 Strength’s
 Minimized bias by
undergoing randomization,
complete follow up, and
intent to treat analysis
 The data can be generalized
in other ICU’s due to
performing the study in 20
different ICU’s
 Limitations
 The results were obtained for cisatrocurium
only and not other NMBA’s
 Did not asses the use of NMBA’s in the late
course of ARDS
 Absence of data on the conditions known to
antagonize or potentiate neuromuscular
blockade.
 Felt the study was underpowered
 Post-hoc analysis
▪ Beneficial effects of NMBA’s were
confined to those patients who had the
PaO2:FiO2 ratio below 120
▪ about 2/3 of the patients in the study
group

 A very good study method, rigorous blinding process
to patients and investigators
 Treatment groups were appropriately randomized
and were very similar in characteristics at baseline
 The primary and secondary endpoints that were
chosen are in line with other similar clinical trials
 The study brings forth a strong opposition to the idea
set by many authorities that NMBA’s should be
limited in their use in treating patients with ARDS
mainly due to the concern of muscle weakness that
can develop in long-term

 Result obtained from this study may be robust
 In order to make a strong argument of the beneficial effect of the
NMBA”s in reducing mortality, the result of the study must be
reproduced
 The authors had conducted similar trials using the same inclusion
criteria but found that the mortality rate is much lower in the
placebo group of this study compared to the other study
 Unknown whether or not the observed benefit seen by cisatracurium
is specific to cistracurium or shared within the drug class
 Further study is needed to be done, especially when succinylcholine
is more preferred to be used due to it’s quick onset of action and
duration
 The drug should have been compared to other agents in the class to
see it’s benefit in pharmacotherapy in the ICU over the other NMBA’s

 Should be utilized in practice when performing
mechanical ventilation procedure or surgery
 Provides beneficial effects in terms of mortality and
complications from occurring from intubation
 Very good pharmacologic profile compared to the other
types of NMBA’s
 Cardiovascular stability
 Organ independent elimination
 Lack of metabolites with neuromuscular blocking activity
 Reduced rhabdomyolysis

 Nimbex (Package Insert). Abbott Park, IL: Abbott Laboratories; 2008
 Lexi Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp,
Inc.;2007;October 17,2010.
 Medline Plus, NIH. Acute Respitatory Distress Syndrome. Available at
http://www.nlm.nih.gov/medlineplus/ency/article/000103.htm. Accessed on
10/16/2010
 Food and Drug Administration, FDA-Drugs shortages. Available at
http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050792.htm
 Arnal JM., Constantin JM., Courant P., Forel JM., Gacouin A. Guerin C., , Jaber
S., Lefrant JY., Loundou A., Morange S., Papazian L.,Penot-Ragon C., Perez D.,
Perrin G., Prat G., Roch A.Neuromuscular Blockers in Early Acute Respiratory
Distress Syndrome. N England J Med 2010;363(12);1107-16
 Gainnier M., Roch A., Forel JM.,Thirion X., Arnal JM., Donati S., Papazian L.Effect
of neuromuscular blocking agents on gas exhange in patients presenting with
acute respiratory distress syndrome.Crit Care Med 2004;32(1);113-119.

Neuromuscular Blocker In Ards

More Related Content

What's hot (20)

Viewers also liked (20)

Similar to Neuromuscular Blocker In Ards (20)

More from Mmorshed217 (6)

Neuromuscular Blocker In Ards

Editor's Notes