Perioperative Nonopioid - PowerPoint Presentation

Slide1

Perioperative

Nonopioid

Infusions For Postoperative Pain ManagementSlide2

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. Slide3

Noncompetetive

N-methyl-D-aspartate glutamate(NMDA) receptor antagonist

Sodium channel blockerAvailable as racemic ketamine which contains the S(+) and R(-) ketamineHalf life of 80-180 minIts metabolite norketamine has a longer half life and is one third as potent as the parent component

Intravenous Ketamine InfusionSlide4

Analgesic properties at low doses

Does not depress the laryngeal protective reflexes

Does not suppress cardiovascular function in the presence of an intact CNSLess depression of ventilation compared to opioidsMay stimulate respirationUsed in subanesthetic dose as an analgesicPlasma conc. 100 to 150

ng

/ml produces analgesia

Undesirable side effects :Cardiovascular excitation,

psychomimetic side effects, tolerance, accumulation of metabolites, malaise

Intravenous Ketamine InfusionSlide5

Most of the randomized controlled clinical studies on perioperative IV ketamine shows some beneficial effect.

Cervical and lumbar spine surgery:

Ketamine 1 mg/kg bolus83 mcg/kg/h maintenanceResulted 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)Intravenous Ketamine InfusionSlide6

Major abdominal surgery

Loading dose 0.5 mg/kg

Maintenance 2 mcg/kg/minFor 48 h after surgeryResulted in lower morphine consumption than patients with saline infusion. Intravenous Ketamine InfusionSlide7

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.Intravenous Ketamine InfusionSlide8

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.Intravenous Ketamine InfusionSlide9

The role of perioperative ketamine in preventing post 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 allodyniaAt 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. Intravenous Ketamine InfusionSlide10

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. Intravenous Ketamine InfusionSlide11

Results:

Large variations in clinical setting

Small number of patients studiedDifferent ketamine regimensDifferent rout of administrationSome beneficial effects in low dose ketamine infusionImprove the efficacy of epidural analgesiaDoes not seem to have any effect when TIVA is used.

Intravenous Ketamine InfusionSlide12

Lidocaine

has peripheral and central effects for pain relief.

It inhibits leukocyte migration and metabolic activationDecrease albumin extravasation in animal models of chemical peritonitisCentrally 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 cordIntravenous

Lidocaine

InfusionSlide13

Several studies showed the beneficial effect of IV

lidocaine

infusionCassuto studied in abdominal surgeryPatients underwent cholecystectomiesIV bolus of 100 mg lidocaineInfusion at 2mg/minStarting 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.

Intravenous

Lidocaine

InfusionSlide14

Groudine

studied

lidocaine infusion in retropubic prostatectomy patients1.5 mg/kg bolus3mg/min infusionContinued until 1 h postoperativelyLower VASShorter 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

Intravenous

Lidocaine

InfusionSlide15

Two studies not only looked pain relief but the effect of

lidocaine

on markers of inflammation and immune responseSignificant attenuation of the plasma level ofIL-1IL-8Complement C3aIL-1 raCD11bP-selectinPlatelet leukocyte aggregates

Intravenous

Lidocaine

InfusionSlide16

The beneficial effects of IV

lidocaine

infusion were not duplicated in patients who had a total hip replacement or coronary artery bypass graft.Intravenous Lidocaine InfusionSlide17

IV

lidocaine

infusion appears not to be as effective as perioperative epidural analgesiaIntravenous Lidocaine InfusionSlide18

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.

Intravenous

Lidocaine

InfusionSlide19
Slide20

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.Intravenous Naloxone InfusionSlide21

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.

Intravenous Naloxone InfusionSlide22

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. Intravenous Naloxone InfusionSlide23

At higher doses naloxone blocks the action of the released or displaced endorphin at the postsynaptic receptors.

Intravenous Naloxone InfusionSlide24

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. Intravenous Naloxone InfusionSlide25

In summary, it appears that the present indication for IV naloxone infusion is to control the side effects of

neuraxial

opioidsOnly the study of Gan et al showed the efficacy of a low dose naloxone infusion in reducing opioid consumption.Intravenous Naloxone InfusionSlide26

Some surgeons infiltrate the surgical incision with 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.Local anesthetic wound infusionsSlide27
Slide28

A qualitative and quantitative review of the literature on local anesthetic wound infusions concluded that the available

d

ata 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.Local anesthetic wound infusions