








































Anesthesia eJournal
Volume 4 - Issue 1 2016

AEJ

Educated Hand Publishing LLC 
“The Science Behind the Art”  

 Anesthesia eJournal - Online
ISSN 2333-2611

Page 1

Potentiation of a Neuromuscular Blocking Agent Postoperatively by a Polypeptide Class 
Antibiotic: A Case Report
Jenna Reeve, CRNA, DNP
Texas Christian University, 
Dr Reeve was a student at the time of writing the manuscript.

INTRODUCTION
Neuromuscular blocking agents (NMBAs) are administered as part of a general anesthetic to provide muscle relaxation 

during surgical procedures. Examples of commonly administered NMBAs are succinylcholine, rocuronium, vecuronium, 
and cisatracurium. Other medications administered during the surgical procedure may interact with NMBAs.1-12 For 
example, some antibiotics are known to potentiate the effects of NMBAs. Antibiotics are also commonly administered 
to surgical patients during the perioperative period as a prophylactic measure for postoperative surgical wound infections 
or are given intraoperatively as part of continued treatment or for a newly identified infection risk. Although most 
antibiotics work by altering the membrane permeability of bacterial cells, they can also affect the neuromuscular junction 
by causing neuromuscular blockade.1-13

The polypeptide class of antibiotics has been identified as one group of antibiotics that can potentiate NMBAs when 
administered during the perioperative period.1-12 This classification of antibiotics is thought to act at 2 independent 
locations of the neuromuscular junction.1,2,4,10,12 Presynaptically, polypeptide antibiotics reduce the release of acetylcholine. 
Additionally, polypeptide antibiotics inhibit the acetylcholine from reaching its specific receptor postsynaptically. This 
potentiating action of polypeptide antibiotics may make it challenging to reverse a neuromuscular block.

Although a specific medication or therapy to fully reverse antibiotic-induced neuromuscular blockade has not yet 
been discovered, researchers have attempted to reverse the neuromuscular blockade produced from the combination of 
polypeptide antibiotics and NMBAs with calcium chloride and anticholinesterase medications.1,3,4,7-13 These attempts 
have been shown to be inadequate and may only temporarily reverse the block or may adversely prolong the duration of 
the block.1,3,4,7-13 Time and ventilatory support are the only proven treatment for full recovery of neuromuscular blockade 
prolonged by this interaction.1-13 Although the incidence of antibiotic-induced neuromuscular blockade is rare, it is 
important to be aware of this medication interaction and to know how to manage this potential complication.8 This 
report presents one such case with a review of the literature.

Abstract
During multiple surgical procedures, neuromuscular blocking agents (NMBAs) are administered as part of a general 

anesthetic to provide muscle relaxation. Examples of commonly administered NMBAs are succinylcholine, rocuronium, 
vecuronium, and cisatracurium. Administration of other medications during the surgical procedure can cause unexpected 
interactions, such as affecting the action of the NMBAs. The polypeptide class of antibiotics has been identified as one 
group of antibiotics that can potentiate NMBAs when administered during the perioperative period. Although the 
incidence of antibiotic-induced neuromuscular blockade is rare, it is important to be aware of this medication interaction 
and to know how to manage this potential complication. This report presents one such case with a review of the literature.



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016  Page 2

CASE REPORT
A 45-year-old, 152-cm, 121-kg woman was admitted for an 

emergent laparoscopic appendectomy. The patient had abdominal 
pain for approximately 2 days prior to admission but had 
attributed the pain to her menstrual cycle. The patient denied 
any previous surgeries or procedures. Her past medical history 
was significant for benign essential hypertension, but she was not 
taking any prescribed medications for this condition. Recent and 
relevant laboratory data included a white blood cell count of 18.32 
x 100/L. This laboratory value was elevated and was consistent 
with the diagnosis of appendicitis.

The patient’s physical status was scored as American Society of 
Anesthesiologists (ASA) IIE related to the following conditions: 
chronic hypertension, body mass index greater than 40 kg/m2, 
and scheduled for an emergent surgery. A Mallampati score of 
3 and a thyromental distance of 3 finger breadths were noted 
during assessment of the airway with the patient in the upright 
and sitting position. Range of motion capabilities were assessed 
and determined to be nonrestrictive. The patient was complaining 
of abdominal pain with nausea and vomiting. On the basis of 
the patient’s current condition, a general anesthetic with an 
endotracheal tube utilizing a rapid-sequence induction was 
determined to be the best anesthetic plan. In the preoperative 
area, metronidazole 500 mg and piperacillin-tazobactam 4.5 g 
were administered intravenously to help mitigate any potential 
infection risk associated with the patient’s ruptured appendix. 
Morphine sulfate 5 mg was also administered intravenously to the 
patient prior to surgery to assist with pain relief. The patient was 
given 1 L of Lactated Ringers IV prior to induction to increase 
intravascular fluid volume and to help to prevent hypotension 
during induction. Before leaving the preoperative area, the patient 
received famotidine 40 mg to reduce gastrointestinal pH.

In the operating room, a pulse oximeter probe, an automatic 
blood pressure cuff, and electrocardiogram pads were placed on 
the patient. Oxygen was delivered via a facemask at a rate of 
10 L/min once the patient was appropriately positioned on the 
operating table. Vital signs were assessed and were within the 
patient’s normal range. An intravenous induction was performed 
with fentanyl 100 mcg, lidocaine 50 mg, propofol 160 mg, 
succinylcholine 100 mg, and rocuronium 50 mg, while cricoid 
pressure was held, to assist with the rapid-sequence intubation. 
An endotracheal tube was smoothly and successfully inserted 
in one attempt under direct laryngoscopy. Cricoid pressure was 
released after correct endotracheal tube placement was confirmed 
by auscultating bilateral breath sounds. Desflurane was chosen 
as the maintenance anesthetic, with end-tidal concentrations 
maintained at 5.2%. Rocuronium 25 mg was given 4 minutes 
after induction, when 4 twitches were present, prior to incision 
to provide sufficient muscle relaxation. No further rocuronium 
was given. Controlled ventilation was maintained throughout the 
surgical procedure with ventilation settings of 600 mL for tidal 
volume and a respiratory rate of 13 breaths per minute. The end-
tidal CO2 reading was approximately 35 to 38 mm Hg throughout 
the procedure. Before the completion of surgery, a lavage of the 
peritoneum was performed with an irrigant containing polymyxin 
b and bacitracin. A total of 100 mcg of fentanyl was given for the 
entire surgical case. 

Three out of 4 twitches at the patient’s corrugator supercilii 
muscle were present upon assessment of train-of-four with a 
peripheral nerve stimulator at the end of the case. When the 
abdomen was no longer insufflated, neuromuscular blockade 
was reversed with a maximal dose of neostigmine (5 mg), along 
with glycopyrrolate (0.8 mg). The patient began spontaneously 
breathing within a few minutes of reversal at 12 breaths per 
minute with an unassisted tidal volume of 350 to 450 mL. Two 
doses of labetalol 5 mg were also administered intravenously 
upon emergence because the patient’s blood pressure increased 
to 165/92 mm Hg. The patient was successfully extubated after 
confirming a 5-s head lift and after appropriate responses to 
verbal commands were performed. The entire anesthetic and 
surgical procedure were uneventful except for the treatment of 
hypertension during emergence from anesthesia.

Immediately after the patient was transferred to the hospital 
bed with full assist of the operating room staff, respiratory 
weakness was noted. Two-person assisted ventilation was initiated. 
The patient was responding to verbal commands and was able 
to move her upper and lower extremities with some weakness 
noted. However, she could not lift her extremities for more than 
3 to 4 s. She could open her eyes but could not appropriately 
track movement. The anesthesiologist involved in the case was 
notified. Thirty minutes after extubation, naloxone 0.04 mg was 
administered intravenously to determine whether the noted 
respiratory weakness was due to excessive narcotics. However, no 
apparent change in respiratory rate or effort was seen. The end-
tidal concentrations of desflurane were noted to be 0.0% at this 
time. Ten minutes after the initial naloxone dose, an additional 
dose of 0.08 mg was given intravenously. The patient continued to 
follow some commands appropriately, but was only able to exert a 
tidal volume of 30 mL when not assisted. Doxapram 40 mg was 
administered intravenously 5 minutes after the second dose of 
naloxone, followed by a second dose of 80 mg intravenously 10 
minutes later. At this time the anesthesiologist went to discuss the 
current situation with the patient’s husband to determine if any 
recreational drug use had occurred recently. The husband reported 
that the patient had smoked marijuana 2 days before the surgical 
date.

After the second dose of doxapram it was determined that the 
patient would require ventilator assistance and a size 4 laryngeal 
mask airway was successfully inserted. Although no additional 
anesthetic was administered before laryngeal mask airway 
insertion, the patient did not show any signs of discomfort or 
have any changes in vital signs upon device insertion. The patient’s 
condition was reported to an intensive care unit registered 
nurse. Because an intensive care unit bed was not yet available, 
the laryngeal mask was removed and an endotracheal tube was 
inserted to better protect the patient’s airway.

While waiting in the operating room for a bed to become 
available, the patient began to cough, purposefully reach for the 
endotracheal tube, and produced adequate tidal volumes. The 
patient was subsequently extubated. Within 5 of minutes of 
extubation, the patient once again began to have reduced tidal 
volumes. A nasal trumpet was inserted and two-person mask 
ventilation was initiated. The patient had spontaneous eye opening, 
with no tracking, but showed weakness when attempting to follow 



verbal commands. The patient was re-intubated, started on a 
propofol drip, and was transported to the intensive care unit. Her 
vital signs remained stable during transport, and ventilation with 
100% oxygen was assisted with a manual resuscitator. Ventilator 
settings in the intensive care unit were SIMV (synchronized 
intermittent-mandatory ventilation) with a minimum of 8 
respirations per minute. Twenty minutes after arrival to the 
intensive care unit, the patient was extubated. The patient was 
able to effectively, spontaneously breathe without supplemental 
oxygen only 12 hours after being admitted to the intensive care 
unit. Twenty-four hours later, the patient was discharged home in 
stable condition without sequelae.
DISCUSSION

Antibiotics and NMBAs are often administered to patients 
undergoing surgery requiring muscle relaxation. Antibiotics can 
be administered by the anesthesia provider or by the surgeon. 
The type of antibiotic given varies depending on the type of 
surgery, the presence of infection, and the allergies of the patient 
undergoing the surgical procedure. The effects of different 
antibiotics on a cell membrane’s permeability are relatively 
well understood. However, the effects of certain antibiotics at 
the neuromuscular junction are still being researched and may 
be unpredictable.  Muscle relaxation during surgery can be 
achieved by using NMBAs such as rocuronium, succinylcholine, 
vecuronium, and pancuronium.

The patient in this case had a neuromuscular block initially 
produced by succinylcholine and then rocuronium. Blockade 
from the succinylcholine was ruled out when 4 twitches were 
noted prior to the second dose of rocuronium. The neuromuscular 
blockade may have been prolonged when the polymyxin and 
bacitracin irrigant was administered and then further enhanced 
with neostigmine. Before the reversal agents were administered 
to this patient, 3 out of 4 twitches for train-of-four were present, 
with sustained tetany that included fade. Polymyxin, when 
administered alone, can cause fade upon train-of-four assessment, 
but will not show depression during assessment of tetanus.1,3,6,12 
Also, 4 out of 4 twitches can be seen with 70% of cholinergic 
receptors blocked or occupied.12

Some antibiotics have been shown to augment nondepolarizing 
muscle relaxants by enhancing the neuromuscular block.1-13 
Polymyxins, along with other antibiotics, can have a synergistic 
effect on neuromuscular blockade produced by various muscle 
relaxants.1,4,6-12 Polymyxins, bacitracin, and daptomycin are all 
examples of polypeptide antibiotics. Polymyxins have also been 
shown to cause muscle weakness when administered without any 
NMBA.1-2,5-7,9-10,12

Polymyxin affects the neuromuscular junction at both the 
presynaptic and the postsynaptic level. At the presynaptic 
level it decreases the amount of acetylcholine released.1-6,12 At 
the postsynaptic level it blocks acetylcholine from entering 
specific receptor channels.1-6,12 Each of these alterations at the 
neuromuscular junction has an effect on the action potentials in 
muscle tissue and nervous tissue. The polypeptide antibiotics affect 
the postsynaptic junction by noncompetitively antagonizing the 
acetylcholine-active channels on the endplate.2,4-5,10,12 An additive 
effect occurs when polypeptide antibiotics are administered 

with an NMBA because the 2 types of drugs are acting on the 
same site. Thus, if the cholinergic receptors at the postsynaptic 
junction are occupied with the NMBA, the antibiotics can have a 
synergistic effect with the muscle relaxants by also being capable 
of affecting the presynaptic junction.12

Although the specific method of action by which polypeptide 
antibiotics affect acetylcholine release and their receptor channels 
is not completely known, some studies have compared the actions 
of this antibiotic class to the actions of magnesium.2,4,12 At the 
neuromuscular junction, magnesium antagonizes calcium.2,4,12 
Calcium is necessary for acetylcholine to be released.2,4,12 
Therefore, magnesium inhibits the release of acetylcholine from 
the presynaptic junction.

A few studies have revealed that the ED50, which is the dose 
that is effective in at least 50 percent of people, is significantly 
decreased when NMBAs are combined with certain antibiotics.6,12 
Therefore, if a polypeptide antibiotic and an NMBA are both 
required during the perioperative period, the anesthesia provider 
and the surgeon should discuss possibly decreasing the dosage of 
one of these drugs. Decreasing the dosage of the NMBA or the 
antibiotic will decrease the intensity of the block. Furthermore, it 
is important to recognize that polymyxin can not only potentiate 
the neuromuscular blockade produced by an NMBA but also 
cause some degree of neuromuscular blockade when administered 
alone.1-2,5-7,9-10,12 Lindesmith et al9 in 1968 discussed cases in which 
patients experienced symptoms of neuromuscular toxicity due to 
polypeptide antibiotics without being given any NMBA or other 
potentially neurotoxic antibiotics. The polypeptide antibiotics were 
administered intramuscularly to most of the patients.9 Also, to 
prevent possible complications, polypeptide antibiotics and certain 
NMBAs should be used cautiously in patients with altered renal 
function or myasthenia gravis.8 These patient populations are at 
higher risk for neurotoxicity and nephrotoxicity after polypeptide 
antibiotic administration.8

Reversal of neuromuscular blockade caused by antibiotics 
is difficult, and attempts to reverse with calcium chloride and 
cholinesterases have not proven effective.1,3-4,6-12 Although 
neostigmine is an acetylcholinesterase inhibitor, it can actually 
augment the neuromuscular blockade enhanced by polypeptide 
antibiotics.6 Subclinical doses of acetylcholinesterase inhibitors 
may inadequately antagonize neuromuscular blockade and 
actually enhance the blockade at standard reversal dosages.1,3,6,7 
This insufficient antagonizing of the neuromuscular blockade by 
neostigmine is seen only when nondepolarizing muscle relaxants 
are utilized.1,3-4,6-12 Conversely, no change in the neuromuscular 
blockade intensity is seen after neostigmine administration when a 
depolarizing muscle relaxant is utilized.3,12 This difference is likely 
due to the NMBA structure when binding to cholinergic receptors 
on the postsynaptic junction of the neuromuscular junction.3,7,12

Another method of attempting to reverse this type of 
neuromuscular block is the administration of calcium 
chloride.1,3,7,12 Calcium chloride has been shown to only 
temporarily improve the neuromuscular reversal.1,3,7,12 Calcium 
levels that cause hypertension, tachycardia, and arrhythmias 
have been shown to not completely reverse this type of block.3 
This temporary reversal could be due to how polypeptide 
antibiotics affect the neuromuscular junction at 2 independent 

Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016  Page 3



Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016 Page 4

levels.1-6,12 Administering calcium chloride increases the release 
of acetylcholine at the presynaptic junction of the neuromuscular 
junction.1,2,4,12 However, increased levels of calcium chloride do 
not affect the polypeptide antibiotic at the postsynaptic junction 
of the neuromuscular junction because the calcium chloride acts as 
a noncompetitive antagonist to acetylcholine at the acetylcholine-
activated channels of the endplate.3,7,12 Calcium chloride as a 
reversal, although partially effective, may not be the best choice 
because the patient is likely to experience muscle weakness 
again shortly after initial recovery.13 Also, calcium chloride 
administration could antagonize the antibiotic’s antibacterial 
effect.13

Whether an NMBA is administered in addition to a 
polypeptide antibiotic or administered alone, it is commonly 
recommended to administer a reversal agent for neuromuscular 
blockade caused by an NMBA.14 Although immediate recovery 
from neuromuscular blockade caused by NMBAs is difficult to 
achieve, not administering a reversal agent after an NMBA can 
cause residual weakness.14 Also, confirming the presence of at 
least one twitch with a neuromuscular twitch monitor is necessary 
before administering the reversal agent to prevent further residual 
weakness. Without at least one twitch, the patient is at risk for 
residual paralysis once the reversal agent is no longer at the 
neuromuscular junction.14 The commonly used reversal therapy 
for nondepolarizing NMBAs is neostigmine. It is recommended 

that 0.04 to 0.07 mg/kg be administered to assist in the reversal 
of neuromuscular blockade, depending on the patient’s train-of-
four ratio.14 The greater the number and intensity of twitches, the 
less the amount of reversal needed.14 Another cause of residual 
paralysis could be from overdosing a reversal agent, such as 
neostigmine. Neostigmine acts by binding to the same receptor as 
the nondepolarizing neuromuscular blockers and would then cause 
further muscle weakness.14

Although it is standard treatment to administer reversal agents 
for patients who receive nondepolarizing NMBAs, it is also 
difficult to determine how much of the neuromuscular block 
is due to the nondepolarizing NMBA and how much is due to 
the polypeptide antibiotic. The known recovery time for a block 
caused by both, NMBAs and polypeptide antibiotics, or by only 
polypeptide antibiotics has yet to be discovered. The necessary 
recovery time can vary widely depending on the antibiotic and 
NMBA administered. Therefore, ventilation should be controlled 
in a patient who has received cyclic peptide antibiotics and muscle 
relaxants until standard requirements for extubation have been 
met and no signs of neuromuscular weakness are seen. These steps 
will decrease future unnecessary airway manipulation, irritation, 
and injury from re-intubations. Additionally, during this recovery 
period, no further additional doses of neostigmine should be 
administered to prevent further muscle weakness.



REFERENCES
1.  Kronenfeld MA, Thomas SJ, Turndorf H. Recurrence of neuromuscular blockade after reversal of vecuronium in a patient 

receiving polymyxin/amikacin sternal irrigation. Anesthesiology. 1986;65(1):93-94. http://dx.doi.org/10.1097/00000542-
198607000-00019.

2.  Durant NN, Lambert JJ. The action of polymyxin B at the frog neuromuscular junction. Br J Pharmacol. 1981;72(1):41-47. 
http://dx.doi.org/10.1111/j.1476-5381.1981.tb09102.x.

3.  Lee C, Chen D, Nagel EL. Neuromuscular block by antibiotics: polymyxin b. Anesth Analg. 1977;56(3):373-377. http://dx.doi.
org/10.1213/00000539-197705000-00012.

4.  Singh YN, Marshall IG, Harvey AL. Pre- and postjunctional blocking effects of aminoglycoside, polymyxin, tetracycline, and 
lincosamide antibiotics. Br J Anaesth. 1982;54(12):1295-1306. http://dx.doi.org/10.1093/bja/54.12.1295.

5.  Fiekers JF. Neuromuscular block produced by polymyxin B: interaction with end-plate channels. Eur J Pharmacol. 
1981;70(1):77-81. http://dx.doi.org/10.1016/0014-2999(81)90435-0.

6.  Van Nyhuis LS, Miller RD, Fogdall RP. The interaction between d-tubocurarine, pancuronium, polymyxin B, and neostigmine 
on neuromuscular function. Anesth Analg. 1976;55(2):224-228. http://dx.doi.org/10.1213/00000539-197603000-00021.

7.  Fogdall RP, Miller RD. Prolongation of a pancuronium-induced neuromuscular blockade by polymyxin B. Anesthesiology. 
1974;40(1):84-87. http://dx.doi.org/10.1097/00000542-197401000-00022.

8.  Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care. 2006;10:1-13. 
http://dx.doi.org/10.1186/cc3995.

9.  Lindesmith LA, Baines RD Jr, Bigelow DB, Petty TL. Reversible respiratory paralysis associated with polymyxin therapy. Ann 
Intern Med. 1968;68(2):318-327. http://dx.doi.org/10.7326/0003-4819-68-2-318.

10.  Sobek V. Arrest of respiration induced by polypeptide antibiotics. Arzneimittelforschung. 1982;32(3):235-237.
11.  Pittinger C, Adamson R. Antibiotic blockade of neuromuscular function. Annu Rev Pharmacol. 1972;12(1):169-184. http://

dx.doi.org/10.1146/annurev.pa.12.040172.001125.
12.  Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF. Mutual potentiation of the neuromuscular effects 

of antibiotics and relaxants. Anesth Analg. 1979;58(2):107-115. http://dx.doi.org/10.1213/00000539-197903000-00010.
13.  Hasfurther DL, Bailey PL. Failure of neuromuscular blockade reversal after rocuronium in a patient who received oral 

neomycin. Can J Anaesth. 1996;43(6):617-620. http://dx.doi.org/10.1007/BF03011775.
14.  Brull SJ, Murphy GS. Residual neuromuscular block: lessons unlearned. part II: methods to reduce the risk of residual weakness. 

Anesth Analg. 2010;111(1):129-140.

Anesthesia eJournal                         www.anesthesiaejournal.com
Volume 4 - Issue 1 2016  Page 5


