





























AEJ2

ProPofol and Ketamine for targeted  
muscle reinnervation after limb  
amPutation: a case rePort

Angela Hupman, BSN, SRNA 
Ladan Eshkevari, PhD, CRNA

Keywords

propofol, ketamine, TIVA, targeted muscle reinnervation,  
phantom limb pain.

AbstrAct 
Surgical procedures that require neuromuscular monitoring 

present unique challenges to the anesthesia provider. Specific 
patient characteristics such as phantom limb pain or chronic 
opioid use can further complicate perioperative management. The 
following case presentation illustrates the anesthetic management 
of a patient exhibiting these complications who presented for 
surgery with a prior transhumeral amputation. Nerve reassign-
ment was planned with the eventual goal of a thought-controlled 
prosthesis. Anesthesia was maintained by the combination of 
propofol and ketamine along with adjuncts such as hydromor-
phone, midazolam and glycopyrrolate. These drugs and similar 
anesthetic combinations cause minimal changes to neurophysi-
ologic monitoring while decreasing various types of neuropathic 
pain and provide an effective alternative for treating patients with 
chronic pain.  



3Volume 2, No. 1

IntroductIon

Targeted muscle reinnervation (TMR) is a ground-breaking 
procedure that gives upper extremity amputees the ability to 
control prosthetic limbs via reassigned nerves. Approximately 
50 such procedures have been performed worldwide, and the 
following case is the second to have been implemented at a large, 
metropolitan research hospital. Instead of relying on residual 
muscle strength alone, TMR allows for movement stimulated 
by electromyogram (EMG) nerve signals.1 Prostheses are then 
controlled by simply thinking about desired actions- a process 
closely resembling life prior to amputation.1 Choice of intra-
operative anesthetic plays a considerable role both during and 
after the procedure. Total intravenous anesthesia (TIVA) shows 
tremendous ability to reach surgical and patient specific goals in 
regard to effective neuromonitoring and pain control. 

cAse summAry  
A 49-year-old, 63 kg man presented for TMR after a motor 

vehicle accident that resulted in a transhumeral amputation. The 
following nerve transfers were planned: median to clavicular head 
of pectoralis major, ulnar to sternal head of pectoralis major, 
and radial to coracobrachialis. Past surgical history included a 
posterior cervical spine fusion of C5-C6, as well as a rod place-
ment in the right lower extremity. The patient suffered permanent 
contracture of the lower extremities as well as left upper extrem-
ity phantom limb pain. Each of the following medications were 
prescribed 3 times per day:  methadone 20 mg, carisoprodol 
350 mg, baclofen 20 mg, gabapentin 600 mg, and nortriptyline 
50 mg. Every 4 hours, 10 mg of oxycodone was prescribed as 
needed and was taken at regular intervals daily. The preoperative 
chemistries, hematological values and coagulation profile were all 
within normal limits. Vital signs were as follows: blood pressure 
119/60 mm Hg, normal sinus rate at 100 beats/min, respiratory 
rate of 16 breaths/min, saturation of peripheral oxygen (Sp02) 
100% (room air), pain score 7/10 (chronic, sharp). In the preop-
erative holding area, 2 mg midazolam were administered via an 
existing 20 gauge intravenous (IV) catheter.



AEJ4

Upon entering the operating room, standard monitors were 
placed, and 100% oxygen (O2) at 12 L/min was simultaneously 
delivered to the patient by face mask. After an initial set of vital 
signs was obtained, IV anesthetic induction was initiated with 
lidocaine 100 mg, propofol 120 mg, and ketamine 100 mg. 
Due to the patient’s prior cervical spine injury, neck flexion and 
extension were avoided during supraglottic insertion of  a size 
5 laryngeal mask airway (LMA). An end tidal carbon dioxide 
measurement of 36 mm Hg was present upon the third breath, 
and air movement was auscultated bilaterally and equally. The 
O2 flow rate was decreased to 3 L/min, and the LMA was secured 
prior to 90 degree rotation of the operative table. The airway was 
reassessed. An 18 gauge peripheral IV was aseptically placed in 
the right antecubital fossa. 

General anesthesia was maintained with a mixture of propo-
fol 50 ml (10 mg/ml) and ketamine 0.5 ml (100 mg/ml). The 
infusion was initiated at a rate of 80 mcg/kg/min and titrated 
to 110 mcg/kg/min based upon response to surgical stimu-
lus. A concurrent one-time dose of glycopyrrolate 0.2 mg was 
also administered. Intermittent doses of hydromorphone were 
given according to sympathetic response, for a total of 6 mg 
throughout the case. Spontaneous respirations resumed and were 
maintained between 8 and 15 breaths/min. The systolic blood 
pressure ranged from 100 to 125 mm Hg, and the heart rate was 
between 95 and 105 beats/min. For the duration of the case, Sp02 
remained 100% with an intraoperative fraction of inspired O2 

of 0.5. The patient did not receive neuromuscular blockers at 
any point. Ondansetron 4 mg was also given. Neuromonitoring 
was conducted via EMG, motor evoked potentials (MEPs), and 
somatosensory evoked potentials (SSEPs) by a technician.

Upon emergence, the patient was transported to the postanes-
thesia care unit with O2 delivery by simple face mask at 6 L/min. 
The patient denied pain, nausea, or recall of the procedure. There 
were no untoward events. The patient recovered in the hospital 



5Volume 2, No. 1

for a single day, was discharged home, and had tentative plans to 
be fit for prosthesis in 6 months. 

dIscussIon

The anesthetic combination of propofol and ketamine was 
chosen for its beneficial impact on pain management and based 
on the need for neuromonitoring. Procedures that require neuro-
physiologic monitoring of motor activity by way of MEPs and 
EMGs dictate that neuromuscular blocking agents be used judi-
ciously. Train-of-four twitch height should be maintained around 
30% or, clinically, 1 to 2 twitches.2 In contrast, SSEP monitoring 
involves purely sensory-evoked information, and in such cases, 
skeletal muscle contraction and neuromuscular blocking agents 
do not need to be tightly regulated.2 Since motor function was of 
concern, neuromuscular blocking agents were not used during 
this case. For further discussion, most anesthetic agents, not just 
those acting at the neuromuscular junction, can either suppress 
or enhance both the amplitude and latency of waveforms being 
recorded.3

Halogenated volatile anesthetics produce a dose-dependent 
decrease in amplitude and increase in latency of MEP signals.3 
Wang et al. reiterate this concept and describe that at levels 
greater than 0.5 minimum alveolar concentration (MAC), inha-
lational anesthetics produce great variability in neurophysiologic 
readings.3 While use of propofol can also induce a dose-depen-
dent effect similar to volatile anesthetics, the impact is much less 
severe, and the agent provides stable neuromonitoring conditions. 
Additionally, the use of ketamine in conjunction with propofol 
has been shown to enhance signal waveforms.3 It is important to 
recognize that no matter the technique chosen, low MAC inha-
lational agent, TIVA, or a combination of both, abrupt changes 
in the concentration of these agents can challenge the validity of 
results and cause misinterpretation of the information provided.3  

Changes to the anesthetic technique should be avoided if possi-
ble, and when initiated, the changes should be communicated 



AEJ6

with the surgical team and the neuromonitoring technician. 

Phantom limb pain is particularly hard to control and not well 
understood. It is believed that N-methyl-D-aspartate (NMDA) 
receptors play a critical role in this pain pathway.4 Since this is 
the same receptor antagonized by ketamine, its use with vari-
ous types of neuropathic pain has been investigated. Alviar et 
al. studied various pharmacologic interventions for this pain 
pathway and found dichotomous results in regard to ketamine’s 
benefits. While the agent did provide a significant amount of 
analgesia, the less desirable effects produced by dissociation of 
the thalamocortical and limbic systems led to increased secre-
tions, hallucinations, loss of consciousness and sedation.4 With 
similar findings, Sigtermans et al. evaluated the use of ketamine 
in decreasing symptoms of  patients suffering from continuing 
pain, hyperalgesia, and allodynia. In the randomized, double-
blind, placebo-controlled study, 60 patients received either an 
infusion of low-dose ketamine or normal saline over 5 days and 
were followed for 12 weeks.5 According to the study findings, 
the low-dose ketamine infusion resulted in clinically significant 
reductions in pain for 11 weeks as compared to the placebo, 
but it also caused psychomimetic side effects, headache, and 
nausea.5 For all of these reasons, in this case, prior to ketamine 
administration, midazolam was given as a premedication to offset 
potential emergence delirium, and glycopyrrolate was given in 
conjunction to decrease muscarinic side effects. The patient did 
not report any phantom pain immediately postoperatively, nor 
did he have hallucinations. 

Patients suffering from chronic pain undeniably present a 
challenge with respect to controlling perioperative discomfort. 
Suboptimal relief is often encountered, especially with high doses 
of opioid taken on a long-term basis. Loftus et al. suggest that 
perhaps the best way to treat an opioid-dependent patient is by 
tapping into opioid-independent pathways.6 In a randomized, 
double-blind, placebo-controlled study, the researchers evaluated 



7Volume 2, No. 1

patients with chronic pain undergoing major spine surgery, all 
of whom had been taking opioids for a minimum of 6 weeks.  
Results indicated that patients in the treatment group, receiving 
ketamine, required decreased doses of opioid intraoperatively, 
immediately postoperatively, and at 6 weeks post-procedure 
(24% P = 0.006, 37% P = 0.029,  and 71% P = 0.041 less 
opioid, respectively).6 Of note, reductions in analgesic require-
ments did not coincide with any increases in undesirable side 
effects. Loftus et al. conclude that ketamine’s beneficial role in 
treatment of chronic pain is not limited to antagonism of NMDA 
receptors but incorporates other factors such as modulation of 
neurotransmitters associated with depression and reduction of 
opioid mu, kappa and delta receptor sensitization.

conclusIon 
Use of propofol and ketamine for TMR was effective in meeting 

the surgical and anesthetic goals of this case. Neuromonitoring 
was not compromised; the patient was adequately anesthetized, 
and the need for chronic pain control was addressed. Use of 
propofol and ketamine in combination with adjunct medications 
such as midazolam, glycopyrrolate, and hydromorphone proves 
to be a suitable anesthetic plan for this and similar situations. 

The number of patients presenting for care following amputa-
tion will continue to grow. This anesthetic technique may be 
utilized for warriors returning home, those involved in trau-
matic injury, or anyone following the loss of a limb. Amputees 
present following a variety of injuries, and many of them occur 
while serving in the United States military. The New York Times 
recently explained that the utility of TMR for American service 
members is becoming increasingly apparent. More than 1570 
soldiers lost limbs while serving in either Iraq or Afghanistan.7 
These individuals will experience many inconveniences, including 
phantom limb pain and a reduction in overall independence that 
muscle reinnervation may improve. The Marine Corps member 
featured in the article underwent TMR and is now practicing 



AEJ8

daily activities with his new mechanical arm, as well as surfing, 
swimming and kayaking.7 It is important that anesthesia provid-
ers recognize the beneficial impact that these procedures can have 
on an individual’s quality of life and be able to provide effective 
anesthetic management for such cases. 

summAry of Key PoInts

Procedures requiring neuromuscular monitoring present unique 
challenges to the anesthetist. Further complications arise when 
patients suffer from neuropathic or chronic pain. When choosing 
an anesthetic plan to meet these goals, the following key points 
may be considered. 

»» Propofol can cause dose-dependent decreases in amplitude 
and increases in latency; however, the effects are much less 
pronounced than with the use of volatile anesthetic agents. 
The use of propofol allows for fairly stable neuromonitor-
ing conditions. 

»» In contrast to many other anesthetic agents, ketamine 
enhances neuromonitoring waveforms.

»» Ketamine antagonizes NMDA receptors, which are 
believed to play a role in neuropathic and phantom limb 
pain. 

»» Ketamine is an antagonist at various opioid receptors, 
making it an effective alternative in the treatment of 
chronic pain patients. 

»» Regardless of the anesthetic technique employed, the 
provider should not abruptly change the anesthetic when 
neuromonitoring is being utilized. Effective and ongoing 
communication between the anesthesia provider, surgeon, 
and neuromonitoring technician is crucial. 

Author Info

(principal author) Angela Hupman, BSN, Student Registered 
Nurse Anesthetist, Georgetown University Nurse Anesthesia  
Program, Washington, DC. angelahupman@gmail.com, 
(904) 742-6941



9Volume 2, No. 1

(senior and corresponding author) Ladan Eshkevari, PhD, 
CRNA, Nurse Anesthetist, Assistant Director, Professor, George-
town University, Washington, DC. eshkevl@georgetown.edu

references 
1 Kuiken TA, Li G, Lock BA, et al. Targeted muscle reinner-

vation for real-time myoelectric control of multifunction 
artificial arms. JAMA. 2009;301(6):619-628. 
doi: 10.1001/jama.2009.116.

2 Seubert CN, Mahla ME. Neurologic monitoring. In: 
Miller R, ed. Miller’s Anesthesia. 7th ed. Philadelphia, PA: 
Churchill Livingstone; 2010:1477-1541.

3 Wang AC, Than KD, Etame AB, La Marca F, Park P. 
Impact of anesthesia on transcranial electric motor evoked 
potential monitoring during spine surgery: a review 
of the literature. Neurorsurg Focus. 2009;27(4):1-4. 
PMID:19795956.

4 Alviar MJ, Hale T, Dungca M. Pharmacologic interven-
tions for treating phantom limb pain. 2011. The Cochrane 
Library. http://onlinelibrary.wiley.com./doi/10.1002/146

  551858.CD006380.pub2/full. Accessed January 28, 2012. 
5 Sigtermans MJ, van Hilten JJ, Bauer MCR, et al. Ketamine 

produces effective and long-term pain relief in patients 
with complex regional pain syndrome type 1. Pain. 
2009;145(3):304-311. PMID:19604642.

6 Loftus RW, Yeager MP, Clark JA, et al. Intraoperative 
ketamine reduces perioperative opiate consumption in 
opiate-dependent patients with chronic back pain  
undergoing back surgery. Anesthesiology. 2010;113(3):639-
646. PMID: 20693876.

7 Dao J. Learning to accept, and master, a $10,000  
mechanical arm. The New York Times. November 27, 
2012:A1.


