Download Perioperative Nonopioid Infusions For Postoperative Pain

Perioperative Nonopioid Infusions For
Postoperative Pain Management
 Opioids are the most commonly used medications for
perioperative pan control.
 Recent studies evaluated the efficacy of nonopioids,
such as ketamine , lidocaine, and naloxone, as
perioperative infusion to decrease pain after surgery.
 Esmolol and Dexmedetomidine have also been
investigated but these drugs have rarely been
employed for perioperative pain management.
 Noncompetetive N-methyl-D-aspartate
glutamate(NMDA) receptor antagonist
 Sodium channel blocker
 Available as racemic ketamine which contains the S(+)
and R(-) ketamine
 Half life of 80-180 min
 Its metabolite norketamine has a longer half life and is
one third as potent as the parent component
 Analgesic properties at low doses
 Does not depress the laryngeal protective reflexes
 Does not suppress cardiovascular function in the
presence of an intact CNS
 Less depression of ventilation compared to opioids
 May stimulate respiration
 Used in subanesthetic dose as an analgesic
 Plasma conc. 100 to 150 ng/ml produces analgesia
 Undesirable side effects :Cardiovascular excitation,
psychomimetic side effects, tolerance, accumulation of
metabolites, malaise
 Most of the randomized controlled clinical studies on
perioperative IV ketamine shows some beneficial
effect.
 Cervical and lumbar spine surgery:
Ketamine 1 mg/kg bolus
83 mcg/kg/h maintenance
Resulted in lower pain scores less analgesic requirements
and better satisfaction than patients who had saline
infusion or those had lower dose of ketamine
infusion(42 mcg/kg/h)
 Major abdominal surgery
 Loading dose 0.5 mg/kg
 Maintenance 2 mcg/kg/min
 For 48 h after surgery
 Resulted in lower morphine consumption than
patients with saline infusion.
Bilgin et al
 Compared ketamine bolus followed by an infusion
with ketamine bolus alone either before surgical
incision or at wound closure in gynecological
laparotomy patients.
 The patients who had the ketamine bolus and infusion
had lower pain scores and lower morphine
consumption.
 No beneficial effect of the ketamine infusion was
noted when the general anesthetic consisted of total
intravenous anesthesia with remifentanil and propofol
infusion.
 The absence of beneficial effect may be related to the
generous use of opioids intraoperatively.
 The role of perioperative ketamine in preventing post
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amputation pain
Loading dose 0.5 mg/kg
Infusion 0.5 mg/kg/h for 72 h
Was not effective in reducing morphine consumption
or decreasing the stump allodynia
At the 6 month follow up the incidence of phantom
pain and stump pain was 47% in ketamine group
compared to 71% and 35% in the control (saline)
group.
 A ketamine infusion appears to have a salutary effec on
epidural analgesia
 The addition of ketamine infusion to epidural
analgesia in patients who underwent surgery for rectal
adenocarcinoma resulted in less patient-controlled
analgesia, morphine requirements and reduced area of
hyperalgesia.
 Interestingly the patients also had less residual pain
until the sixth postoperative month.
Results:
 Large variations in clinical setting
 Small number of patients studied
 Different ketamine regimens
 Different rout of administration
• Some beneficial effects in low dose ketamine infusion
• Improve the efficacy of epidural analgesia
• Does not seem to have any effect when TIVA is used.
 Lidocaine has peripheral and central effects for pain
relief.
 It inhibits leukocyte migration and metabolic
activation
 Decrease albumin extravasation in animal models of
chemical peritonitis
 Centrally it has been shown to modify the neuronal
responses in the dorsal horn and selectively suppress
synaptic spinal transmission by decreasing C-fiber
evoked activity in the spinal cord
Several studies showed the beneficial effect of IV
lidocaine infusion
 Cassuto studied in abdominal surgery
 Patients underwent cholecystectomies
 IV bolus of 100 mg lidocaine
 Infusion at 2mg/min
 Starting at 30 min before surgery
 Patients had lower pain scores during the first day and
significantly less meperidine during the first 2
postoperative days compared with saline infusion
group.
Groudine studied lidocaine infusion in retropubic
prostatectomy patients
 1.5 mg/kg bolus
 3mg/min infusion
 Continued until 1 h postoperatively
 Lower VAS
 Shorter return of bowel movement
 Shorter hospital stay
 But equal opioids consumption in both groups
The same beneficial effects in Koppert study in major
abdominal surgery
Two studies not only looked pain relief but the effect of
lidocaine on markers of inflammation and immune response
 Significant attenuation of the plasma level of
IL-1
IL-8
Complement C3a
IL-1 ra
CD11b
P-selectin
Platelet leukocyte aggregates
 The beneficial effects of IV lidocaine infusion were not
duplicated in patients who had a total hip replacement
or coronary artery bypass graft.
 IV lidocaine infusion appears not to be as effective as
perioperative epidural analgesia
 The beneficial effects of a perioperative infusion in
abdominal surgery may be related to its ability to
suppress inflammatory process secondary to surgery.
 Also it attenuates proinflammatory cytokines which
induce peripheral and central nervous system
sensitization leading to hyperalgesia.
• These effects are not seen when the trauma is minimal
like ambulatory surgery.
• Also, when there is a moderate component of
neuropathic pain such as total hip or thoracic surgery
these effects are not seen.
 Pure mu receptor antagonist.
 Use with morphine to decrease the incidence of side
effects is intuitive.
 Possibility of reversing the analgesia from the opioid.
 Naloxone infusion has been utilized to decrease the
incidence of nausea, vomiting, respiratory depression,
and urinary retention after epidural and intratechal
opioids.
 A retrospective study in radical prostatectomy patients
showed 0.8 to 1.7 mg intratechal morphine with 5 mcg.kg.h
naloxone IV infusion provided excellent analgesia with
infrequent and minor side effects.
 In a RCT Gan et al assigned 60 patients who underwent
hysterectomy into three groups: PCA morphine with low
dose naloxone, PCA morphine with saline infusion, and
PCA morphine with high dose naloxone infusion. There
was no difference in verbal rating score (VRS) for pain
among the three groups, morphine use was significantly
lower in the low dose group, respiratory depression,
sedation score, hemodynamic parameters, were equal.
 Some investigations noted the biphasic or dual
modulatory effect of naloxone;
The mechanism of analgesic effect of naloxone maybe
related to the release of endorphins or displacement of
endorphins from receptor sites not pertinent to
analgesia,
potentiation of the activity of opioid receptors is another
possibility although this upregulation phenomenon has
been demonstrated after prolonged(7days) naloxone
infusion in animals.
 At higher doses naloxone blocks the action of the
released or displaced endorphin at the postsynaptic
receptors.
 There seems to be no added efficacy when naloxone is
administered via IV PCA.
 THE LACK OF ADDED BENEFIT MAYBE DUE TO THE
DIFFERENT PHARMACOKINETICS OF THE DRUG
WHEN GIVEN INTERMITTENTLY.
 Naloxone has an alpha half-life of 4 min and a beta
half-life of 55 min and a continuous infusion may have
resulted in a constant plasma level resulting in a more
consistent effect.
 In summary, it appears that the present indication for
IV naloxone infusion is to control the side effects of
neuraxial opioids
 Only the study of Gan et al showed the efficacy of a
low dose naloxone infusion in reducing opioid
consumption.
 Some surgeons infiltrate the surgical incision with
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local anesthetics at the end of the operation.
Such practice only result in transient relief .
For the effect to last longer, surgeons infuse the wound
with local anesthetics after the surgery.
These wound infusions have been employed in painful
procedures such as thoracic, cardiac, breast,
abdominal, gynecologic, cesarean section, and spinal
surgeries.
Studies showed the beneficial effects of local
anesthetic wound infusion after thoracic operations.
 A qualitative and quantitative review of the literature
on local anesthetic wound infusions concluded that
the available data consistently showed improved
analgesia across a range of procedures, a very low
technical failure rate, and zero reported toxicity.
 Patient compliance is acceptable and wound infection
rate have not increased.