(PDF) The Perioperative Management of Pain from Intracranial Surgery

REVIEW ARTICLE

The Perioperative Management of Pain from Intracranial Surgery

Allan Gottschalk Æ Myron Yaster

Published online: 1 October 2008

� Humana Press Inc. 2008

Abstract Analgesic therapy following intracranial proce-

dures remains a source of concern and controversy. Although

opioids are the mainstay of the ‘‘balanced’’ general anes-

thetic techniques frequently used during intracranial

procedures, neurosurgeons and others have been reluctant to

administer opioid analgesics to patients following such

procedures. This practice is supported by the concern that the

sedation and miosis associated with opioid administration

could mask the early signs of intracranial catastrophe, or

even exacerbate it through decreased ventilatory drive, ele-

vated arterial carbon dioxide levels, and increased cerebral

blood flow. This reluctance to use opioids following intra-

cranial surgery is enabled by decades of training and

anecdote emphasizing that pain is minimal following these

procedures. However, recent data suggests otherwise, and

raises the question of how to provide safe and effective

analgesia for these patients. Here, this data is reviewed along

with the relevant pain pathways, analgesic drugs and tech-

niques, and the available data on their use following

intracranial surgery. Although pain following intracranial

surgery appears to be more intense than initially believed, it

is readily treated safely and effectively with techniques that

have proven useful following other types of surgery,

including patient-controlled administration of opioids. The

use of multimodal analgesic therapy is emphasized not only

for its effectiveness, but to reduce dosages and, therefore,

side effects, primarily of the opioids, that could be of legit-

imate concern to physicians and affect the comfort of their

patients.

Keywords Craniotomy � Neurosurgery � Analgesia �Analgesics � Opioids � Acute pain

Introduction

Historically, the pain associated with intracranial surgery

has been undertreated because of a presumed lack of need

and a fear that use of opioids, the analgesics most often used

to treat moderate to severe pain, may interfere with

the neurologic examination or lead to its deterioration [1].

Even with the immediate availability of modern imaging

technology, the neurologic exam remains the primary

instrument for perioperative evaluation of patients follow-

ing intracranial surgery. Opioids may produce sedation,

miosis, nausea and vomiting, symptoms that mask or mimic

signs of intracranial catastrophe. Furthermore, opioids, even

when administered in therapeutic doses, may depress minute

ventilation leading to hypercapnia, increased intracerebral

blood volume, and potentially increased intracranial pres-

sure and cerebral edema [2]. Therefore, it is understandable

why physicians involved with the care of these patients are

reluctant to administer opioids. Moreover, why expose a

patient to these risks when there is a presumed lack of need?

Decades of training and anecdote have reinforced a widely

held belief that patients do not experience intense pain

following intracranial surgery, a belief supported by the

fact that surgery on the brain parenchyma per se is not

painful.

A. Gottschalk and M. Yaster are without conflict with respect to the

interventions described in this review.

A. Gottschalk (&) � M. Yaster

Department of Anesthesiology and Critical Care Medicine,

Johns Hopkins Hospital, The Johns Hopkins Medical

Institutions, 600 North Wolfe Street, Baltimore, MD

21287-4965, USA

e-mail: [emailprotected]

Neurocrit Care (2009) 10:387–402

DOI 10.1007/s12028-008-9150-3

Pain Assessment

Pain assessment and management are interdependent and

one is essentially useless without the other. The goal of

pain assessment is to provide accurate data about the

location and intensity of pain, as well as the effectiveness

of measures used to alleviate or abolish it. For the most

part, with the exceptions described later on for special

populations, acute pain can be assessed by self-report with

simple numeric rating scales such as the discrete 0 (no

pain) to 10 (worst imaginable pain) scale that is commonly

used [3]. Direct patient observation is generally insufficient

since even experienced nurses and physicians tend to

underestimate pain particularly when it is most severe [4].

Unpublished data indicates that, at least at the authors’

institution, few physicians involved in the care of neuro-

surgical patients make the necessary formal assessments of

patients’ pain [5]. When patients describe past painful

experience they tend to recall pain intensity as less than

what they reported when they were experiencing the pain

[6, 7]. Furthermore, for reasons which remain unclear,

patients hesitate to make medical staff aware that they are

in pain [8]. Finally, satisfaction with pain-relieving therapy

does not necessarily relate to the effectiveness of that

therapy. As a rule, patients expect perioperative pain [9]

and value even less effective efforts at providing analgesia

[10]. Given these findings, it is easy to see how pain fol-

lowing intracranial surgery might be perceived by surgeons

as less than actually experienced by patients, providing

reassurance to those who would prefer to limit analgesic

therapy for the reasons elucidated above [11].

Pain and Intracranial Surgery

The literature on pain following intracranial surgery is just

beginning to present a sufficiently coherent picture to

reconsider its quality, intensity, and duration. Several

small, early studies demonstrated a period of moderate to

severe pain in 41% [12] to 84% [13] of patients in the first

24 postoperative hours. Studies like these supported a

growing recognition that craniotomy pain was more intense

than physicians believed [1, 14, 15]. On the other hand, a

larger, more recent study was inconsistent with this view

[16]. In this study of pain during admission to the pos-

tanesthesia care unit for periods of time averaging less than

2 h, pain scores on a discrete 0–10 scale averaged less than

1. Whether this was due to residual effects of the opioid-

based anesthetic techniques common during intracranial

surgery or some other factor, these observations fueled the

belief that patients were comfortable following craniotomy.

For many patients in another study, the pain accompanying

intracranial surgery was found to be greater than expected

[17]. Most recently, a large prospective study of pain fol-

lowing major intracranial surgery demonstrated some

period of moderate to severe pain (C4 on a 0–10 scale) in

69% of patients on the first postoperative day and in 48%

of patients on the second [18]. In contrast to studies with

other types of pain [10], patient satisfaction varied signif-

icantly with the quality of pain relief. Similar rates of

moderate to severe pain were also observed in another

more recent study [19]. Demographic and clinical factors

associated with increased pain following intracranial sur-

gery include sex [13, 18], age [13, 18, 19], surgical site

[18–20], surgical approach [21, 22], and use of nerve

blocks [18, 23] or local anesthetic infiltration of the inci-

sion site [24]. Pain intensity is also a significant factor in

studies evaluating the quality of recovery from intracranial

surgery [25].

Although the primary focus of intensivists is the acute

pain which accompanies intracranial surgery, a full

appreciation of the pain associated with intracranial sur-

gery requires recognition of the chronic pain syndromes

that can also occur. This recognition mirrors what is

occurring with other types of surgery, where an increasing

number of surgical approaches are linked with procedure-

specific pain syndromes of varying incidence and impact

[26]. Common factors associated with other types of

surgery include the intensity of postoperative pain and

nerve injury. After supratentorial surgery, the prevalence

of headache one year following surgery was 11% [27].

This is lower than seen with posterior fossa procedures,

where the prevalence of headache one year after surgery

is reported to be about 30% [28, 29]. Whether aggressive

perioperative analgesia could reduce the incidence

of long-term pain following craniotomy, as has been

speculated for other types of surgery [30], remains

unanswered.

Ironically the brain is insensate, and this fact may also

contribute to the notion that pain following intracranial

surgery should be limited. However, the muscles which

attach to the skull, the scalp, the periosteum, and the dura,

can be quite sensitive to noxious stimuli. An understanding

of their innervation can be useful for developing a peri-

operative analgesic regimen to reduce postoperative pain,

and for appreciating the limitations of particular approa-

ches for certain types of surgery. The key nerves (Fig. 1)

arise from all three divisions of the trigeminal nerve and

the first three spinal nerves. They contribute sensation to

the frontalis, temporalis, occipitalis, and cervical muscles

which attach to the occiput, all of which may be manipu-

lated or whose origin on the skull may be interrupted

during intracranial surgery. These same nerves provide

sensation to the scalp and periosteum [31]. Importantly, all

of these nerves are readily accessible for nerve block

(Fig. 1).

388 Neurocrit Care (2009) 10:387–402

Although the same cranial and spinal nerves provide

sensation to the dura, the innervation is less straightforward

and less accessible for neural blockade (Fig. 2) [32]. Cat-

echolaminergic fibers from the dura also originate from the

superior cervical ganglion of the sympathetic chain [33].

Although the innervation of the dura cannot readily be

interrupted with extracranial nerve blocks, knowledge of

these pathways is still important for relieving pain during

awake intracranial surgery. Furthermore, mechanical and

chemical irritation of the dura remaining after surgery can

contribute to painful postoperative sensation, even after an

effective scalp block. Since this pain is referred to the

Fig. 1 Innervation of the scalp and underlying muscles. Sensation is

provided by all three divisions of the trigeminal nerve and the ventral

rami of the 2nd and 3rd cervical nerve roots. The ophthalmic branch

of the trigeminal nerve gives rise to the supraorbital and supratroch-

lear nerves, the maxillary division gives rise to the zygomaticotemoral

nerve, and the posterior trunk of the mandibular division gives rise to

the auriculotemporal nerve. The lesser occipital nerve originates from

the ventral ramus of the 2nd cervical nerve root, whereas the greater

occipital nerve originates from the ventral rami of the 2nd and 3rd

cervical nerve roots. A scalp block sufficient for awake craniotomy or

as an adjunct to general anesthesia can be performed by injections at

the crosshatched regions on the figure. In practice, a bead of local

anesthetic over the medial half of the brow and one initiated just

lateral to the orbit and continued to the occipital prominence is

effective. The specific choice of nerves to block should be

individualized once the surgeon has specified the incision. In addition

to blockade of the nerves supplying sensation to the surgical site, local

anesthetic blockade of the pin sites not otherwise contained by prior

nerve blocks should be performed. A long-acting local anesthetic

(e.g., bupivacaine 0.5%) will maximize postoperative analgesia, but

efforts to avoid potentially toxic doses should be made as large

bilateral incisions can often require 30 ml or more of local anesthetic.

Some surgeons have expressed concern about local anesthetic

injection in the temporal region prior to vascular procedures out of

concern about potential damage to the superficial temporal artery.

Local anesthetic administration in the temporal region close to the

zygoma can also produce an inadvertent block of branches of the

facial nerve and this should be considered in the postoperative

neurologic assessment

Neurocrit Care (2009) 10:387–402 389

corresponding somatic distribution of the associated

nerves, this may help to identify the intracranial region of

concern.

Patient, Anesthetic, and Surgical Factors

Treatment of the pain accompanying intracranial surgery

begins prior to the procedure itself through recognition of

patient-specific issues which influence perioperative man-

agement. As indicated above, a number of demographic

factors such as female sex, younger age, and posterior fossa

approach may predispose patients toward more intense

perioperative pain. Patients with chronic painful conditions

incidental to or associated with the anticipated surgery are

more likely to experience increased perioperative pain [34]

and may already be taking opioid analgesics [35]. For

certain procedures, pain may not simply be a symptom of

Fig. 2 Intracranial innervation of the dura is provided by branches

from all three divisions of the trigeminal nerve and the first three

spinal nerves. As might be anticipated, the pain associated with

noxious stimulation of the dura is referred to the corresponding

somatic distribution of the nerve involved. A tentorial branch of the

ophthalmic division of the trigeminal supplies the tentorium cerebelli

and falx cerebri, coursing posteriorly along the tentorium, ascending

along the falx and traveling anteriorly. These nerves tend to follow

venous structures, providing sensation to the sinuses and the terminal

portion of the veins which drain into them. The most anterior portion

of the falx and base of the anterior cranial fossa are supplied by

meningeal branches of the anterior and posterior ethmoidal branches

of the ophthalmic division of the trigeminal nerve. The remainder of

the supratentorial dura is supplied by a meningeal branch of the

maxillary division of the trigeminal nerve, the nervus meningeusmedius, and a branch of the mandibular division, the nervus spinosus.

The nervus meningeus medius originates just prior to the exit of the

maxillary division of the trigeminal nerve through the foramen

rotundum, whereas the nervus spinosus is a recurrent branch of the

mandibular division which enters the skull through the foramen

spinosum along with the middle meningeal artery. Both of these

meningeal nerves course with the branches of the middle meningeal

artery, and the dura tends to be most sensitive where these vessels are

the most plentiful. The dura of the posterior fossa is supplied by

branches of the first three spinal nerves which enter the cranial vault

through the anterior portion of the foramen magnum and through the

jugular foramen and hypoglossal canal. Although extracranial access

to these nerves for the purpose of neural blockade is not generally

possible, intracranial blockade of the nervus spinosus can be

performed by injecting the dura where the middle meningeal artery

exits the foramen. When pain is experienced during awake craniot-

omies by traction of the dura and associated vascular structures,

identification of the nerve responsible and its blockade is possible by

recalling the anatomy of the tentorial and meningeal nerves, their

association with veins and arteries, respectively, and injecting small

amounts of local anesthetic between the dural layers at an appropriate

location

390 Neurocrit Care (2009) 10:387–402

the underlying disease, but is the criterion which dictates

that surgery should take place. Examples of this are

decompressions of type-I Chiari malformations or micro-

vascular decompression of the trigeminal nerve.

Effective perioperative analgesia also requires knowl-

edge of the anesthetic course and how it could affect the

pain experienced upon the conclusion of surgery. Opioid-

based ‘‘balanced’’ anesthetics are often used for intracra-

nial procedures [36] because of the hemodynamic stability

they confer, their minimal effects on cerebral blood flow,

and their contribution to a prompt and smooth emergence.

The specific opioid, the amount administered, and the

timing of administration with respect to the duration of

surgery and emergence all impact on the level of opioid

analgesia present upon emergence.

Paradoxically, intraoperative opioids may increase

postoperative analgesic requirements, a phenomenon

known as opioid-induced hyperalgesia [37]. This may be

prevented with concurrent administration of the dissociative

analgesic ketamine which is an N-methyl-D-aspartate

(NMDA) antagonist [38]. However, ketamine is rarely used

in neurosurgical patients because it is a hallucinogen that

alters the postoperative sensorium. Recently, it was dem-

onstrated that preoperative gabapentin can also prevent

opioid-induced hyperalgesia [39]. Opioid-induced hyper-

algesia may be a particular problem with remifentanil,

whose short elimination half-life of 3–10 min permits a

large intraoperative opioid effect capable of inducing

hyperalgesia, but with virtually no residual opioid effect

once emergence is complete. Certainly, in one study, when

remifentanil was used as a component of a balanced anes-

thetic technique for supratentorial craniotomy, even in

conjunction with small amounts of morphine sulfate, the

number of patients reporting severe pain in the immediate

postoperative period doubled compared to the fentanyl

group [40]. Another study comparing remifentanil and

fentanyl, as components of a balanced anesthetic technique

for supratentorial craniotomy, demonstrated earlier requests

for analgesics in the remifentanil group [41]. Comparisons

of intraoperative remifentanil–propofol to sufentanil–

propolfol for supratentorial craniotomy revealed only that

patients who received remifentanil requested analgesics

sooner [42]. Furthermore, as nitrous oxide enjoys another

period of disfavor [43] and with remifentanil infusion

already advocated as a means of achieving a brisk emer-

gence without use of nitrous oxide [44], remifentanil use is

becoming more common. Apart from creating a vacuum

that may be filled by other drugs with their specific impact

on analgesia, avoiding nitrous oxide may also avoid its

beneficial analgesic effects [45], some of which may stem

from its properties as an NMDA antagonist [46]. A newer

drug, dexmedetomidine, an a2-agonist administered by

continuous intravenous infusion, was recently introduced, is

currently approved for sedation during awake craniotomy

and is also used for sedation in the setting of the intensive

care unit [47]. It may be useful to recognize the perioper-

ative opiate-sparing effects of this class of drug [48].

Large doses of corticosteroids, generally dexamethasone,

are frequently administered during intracranial surgery.

Consequently, patients experience a powerful antiinflam-

matory effect that may reduce pain as well as an antiemetic

effect [49]. However, the antihyperalgesic effect from

cyclooxygenase-2 (COX-2) inhibition in the spinal cord that

is seen with nonsteroidal antiinflammatory drugs is not

realized [50]. Finally, whether a patient receives a scalp

block or local anesthetic infiltration of the incision site will

influence the intensity and time course of postoperative pain

[18, 23, 24]. Preoperative use of local anesthetic in this

manner can decrease intraoperative anesthetic require-

ments, leading to a brisker emergence and a more

cooperative patient in the immediate postoperative period.

Apart from the actual location of the surgery, a number

of additional surgical factors may influence the pain

experienced afterwards. For example, in the approach to

the posterior fossa, use of a craniotomy as opposed to a

craniectomy [21] and performance of a cranioplasty after a

craniectomy [51] have both been reported to reduce pain,

perhaps by preventing the traction that occurs with post-

operative cervical muscle attachment to the dura. A

translabyrinthine as opposed to a suboccipital approach

was reported to reduce the incidence of pain following

acoustic neuroma resection [22], but these differences were

no longer appreciated one year after surgery [52]. Other

studies were not as favorable concerning the translabyrin-

thine approach [53]. Another surgical factor which may

affect perioperative pain is the extent that branches of

the greater occipital nerve are divided in the approach to

the posterior fossa. It has also been hypothesized that the

amount of muscle damage from resection of the temporalis

muscle for supratentorial craniotomy or splitting of the

posterior cervical muscles for posterior fossa surgery may

largely determine the amount of pain experienced [14].

Overall Analgesic Strategy

Acute pain management in adults and children is increas-

ingly characterized by a multimodal approach in which

smaller doses of opioid and nonopioid analgesics, such

nonsteroidal antiinflammatory drugs, local anesthetics,

NMDA antagonists, a2-adrenergic agonists, and other

drugs are combined to target pain at multiple pathways. A

multimodal approach can also utilize nonpharmacologic

complimentary and alternative medicine therapies as well.

These include distraction, guided imagery, massage,

transcutaneous nerve stimulation, and acupuncture.

Neurocrit Care (2009) 10:387–402 391

Combining analgesic techniques and drugs has an additive

or synergistic effect which maximizes pain control, mini-

mizes opioid-induced side effects and, therefore, facilitates

recovery and rehabilitation.

Another important concept about acute pain therapy is

that of ‘‘preemptive analgesia’’ [54–56]. Intense nociceptor

stimulation can lead to central sensitization, the process

whereby neurons of the central nervous system adjust their

dynamic range so that subsequent stimuli are experienced

with greater intensity. Importantly, insofar as perioperative

pain is concerned, this process is ongoing despite otherwise

adequate levels of volatile anesthetics such as isoflurane

[57]. Preemptive analgesic strategies seek to limit central

sensitization during surgery by modulating the response to

noxious input during the perioperative period, thereby

reducing subsequent pain and the level of analgesic therapy

necessary to control it. Of the analgesic modalities relevant

for pain therapy following intracranial surgery, local

anesthetic infiltration, NSAIDs and NMDA antagonists,

but not systemic opioids can lead to measurable preemptive

analgesic effects [30]. It is debatable whether the phe-

nomenon of opioid-induced hyperalgesia described earlier

has, in some circ*mstances, masked the benefits of pre-

emptive systemic opioid administration. Of the available

analgesic therapies, local anesthetic use, as detailed below

and in Fig. 1, is the only one with a demonstrative pre-

emptive analgesic effect following intracranial surgery,

although it is the only one evaluated explicitly for this

effect in this population, thus far.

In the next sections, we will review some of the drugs

and techniques used postoperatively for multimodal pain

treatment and treatment algorithms for many of the most

common opioid-induced side effects. The tools and fun-

damental questions revolving about analgesic therapy

following intracranial surgery are the choice of specific

systemic adjuvants (Table 1), systemic opioids (Table 2),

and nerve blocks (Figs. 1 and 2) along with the route and

method of their administration, timing, and dosage. Sug-

gestions for managing opioid-induced side effects can be

found in the algorithms of Fig. 3 and in Table 3.

Table 1 Oral dosing guidelines for commonly used nonopioid analgesics

Drug (brand name) Dose (mg/kg)

(<50 kg)

Dose (mg)

(>50 kg)

Interval

(h)

Daily

maximum

dose (mg/kg)

(<50 kg)

Daily

maximum

dose (mg)

(>50 kg)

Side effects

Acetaminophen (Tylenol�) 10–15a 650–1,000 4 100a 4,000 Hepatotoxicity with toxic doses,

lacks antiinflammatory activity,

does not interfere with platelet

function

Ibuprofen (Motrin�) 5–10 400–600c 6 40b,c 2,400c Gastrointestinal irritation,

bronchospasm, interferes with

platelet function, hematuria

Ketorolac (Toradol�) 0.5 15–30 6 2b,c 120c See ibuprofen

Naproxend (Naprosyn�) 5–6c 250–375c 12 24b,c 1,000c See ibuprofen

Aspirine 10–15c,e 650–1,000c 4 80b,c,e 3,600c Reye’s syndromee, see ibuprofen

Choline-Mg tri-salicylatef

(Trilisate�)

7.5–15b,c 500–1,000c 4–8 80b,c,e 3,600c Preserves platelet function.

Otherwise, see aspirin

Gabapenting (Neurontin) 10–20 600–1,200 NA NA NA Sedation, dizziness, gait

disturbance

Pregabaling (Lyrica) 5–10 150–600 NA NA NA See gabapentin

a Maximum daily doses for acetaminophen should be reduced to 80 mg/kg in term neonates and infants and to 60 mg/kg in preterm neonates.

Supplied in multiple formulations, e.g., combined with codeine, making accidental overdosage possible. Rectal suppositories availableb Dosing guidelines for neonates and infants have not been establishedc Higher doses may be used in selected cases for treatment of rheumatologic conditionsd Ketorolac is the only parenterally available NSAIDe Aspirin carries a risk of provoking Reye’s syndrome in infants and children. Because it permanently inhibits platelet function aspirin is rarely

prescribed in the immediate postoperative period. If other analgesics are available, aspirin use should be restricted to indications where

antiplatelet or antiinflammatory effect is required, rather than as a routine analgesic or antipyreticf Aspirin-like compound that does not affect platelet adhesiveness or aggregationg Generally administered as a single oral preoperative dose. There is little published perioperative experience in children

392 Neurocrit Care (2009) 10:387–402

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Neurocrit Care (2009) 10:387–402 393

Nonopioid Analgesics

The ‘‘weaker’’ or ‘‘milder’’ analgesics with antipyretic

activity, of which acetaminophen [paracetamol] (Tylenol�),

salicylate (aspirin), ibuprofen (Motrin�), naproxen (Aleve�,

Naprosyn�), diclofenic are the classic examples, comprise a

heterogenous group of nonsteroidal antiinflammatory drugs

(NSAIDs) and nonopioid analgesics (Table 1). They pro-

vide pain relief primarily by blocking peripheral and central

prostaglandin production by inhibiting COX-1 and COX-2.

These analgesic agents are administered enterally via the

oral or, on occasion, the rectal route and are particularly

useful for inflammatory, bony, or rheumatic pain. Paren-

terally administered NSAIDs, such as ketorolac (Toradol�),

are available for use in patients when oral or rectal admin-

istration is not possible. Unfortunately, regardless of dose,

the nonopioid analgesics reach a ‘‘ceiling effect’’ above

which pain can not be relieved by these drugs alone.

Because of this, these weaker analgesics are often admin-

istered in oral combination forms with opioids such as

codeine, oxycodone, or hydrocodone.

Aspirin has been largely abandoned in postoperative

pain management because it permanently inhibits platelet

function, which could have catastrophic consequences in a

patient who has recently undergone intracranial surgery.

On the other hand, choline-magnesium trisalicylate (Trili-

sate�) is an unique aspirin-like compound that does not

bind to platelets and therefore has minimal, if any, effects

on platelet function [58]. This makes choline-magnesium

trisalicylate a potentially useful adjunct in postoperative

analgesia.

The most commonly used nonopioid analgesic in neu-

rosurgical practice remains acetaminophen (paracetamol).

Unlike aspirin and the other NSAIDs, acetaminophen works

primarily centrally and has minimal, if any, antiinflamma-

tory activity. It is also thought to have an analgesic effect by

antagonizing NMDA and substance P in the spinal cord.

When administered in normal doses (10–15 mg/kg, PO),

acetaminophen is extremely safe and has very few serious

side effects. It is an antipyretic and like all enterally

administered NSAIDs, takes about 30 min to provide

effective analgesia. It is often administered alone or in

Fig. 3 Algorithm for relief of common opioid side effects. See Table 3 for drug dosages

394 Neurocrit Care (2009) 10:387–402

combination with oral opioids such as codeine, hydroco-

done, or oxycodone (see below). The ubiquitousness and

sense of safety of acetaminophen sets up the possibility of

excessive and potentially hepatotoxic acetaminophen dos-

ing, particularly when combination preparations such as

Tylox� or numbered Tylenol� are given for uncontrolled

pain or when they are ordered in addition to previously

prescribed acetaminophen. This problem was seen in our

study of analgesic use following craniotomy [18]. Regard-

less of preparation(s), the daily adult maximum

acetaminophen dose is 4000 mg/day (Table 1). Finally, an

intravenous formulation of acetaminophen is now available

in Europe and can be used in patients in whom the enteral

route is unavailable. This formulation has been associated

with better analgesia than oral acetaminophen in clinical

trials in adult patients and is equally effective and less

painful than the ‘‘pro’’ formulation of the drug in children

[59]. It is under investigation in the United States and

hopefully will be available for widespread use shortly.

The discovery of at least two COX isoenzymes has

updated our knowledge of NSAIDs [60–63]. The two COX

isoenzymes share structural and enzymatic similarities, but

are specifically regulated at the molecular level and may be

distinguished apart in their functions. Protective prosta-

glandins, which preserve the integrity of the stomach lining

and maintain normal renal function in a compromised kid-

ney, are synthesized by COX-1 [61, 62, 64]. COX-2 is

inducible, and the inducing stimuli include pro-inflamma-

tory cytokines and growth factors, which implies a role for

COX-2 in both inflammation and control of cell growth. In

addition to the induction of COX-2 in inflammatory lesions,

it is present constitutively in the brain and spinal cord, where

it may be involved in nerve transmission, particularly that

for pain and fever. Although the discovery of COX-2 has

made possible the design of drugs that reduce inflammation

without removing the protective prostaglandins in the

stomach and kidney made by COX-1, the growing contro-

versy regarding the potential adverse cardiovascular risks of

prolonged use of the COX-2 inhibitors has dampened much

of the initial enthusiasm for this drug class [65, 66].

Opioid Drug Selection

The potent analgesic drugs are commonly referred to as

‘‘narcotics’’ (from the Greek ‘‘narco’’—to deaden), ‘‘opi-

ates’’ (from the Greek ‘‘opion’’—poppy juice, for drugs

derived from the poppy plant), ‘‘opioids’’ (for all drugs with

morphine-like effects, whether synthetic or naturally

occurring) or, euphemistically, ‘‘strong analgesics.’’ Opi-

oids, the preferred terminology, produce analgesia by

binding to G-protein-coupled receptors (l, j, and d) located

throughout the central and peripheral nervous system as

well as in the gut [67, 68]. The opioids most commonly used

in the management of pain are l agonists and include

morphine, meperidine, methadone, codeine, oxycodone,

and the fentanyls. Many factors should be considered when

deciding which is the appropriate opioid analgesic to

administer to a patient in pain. These include pain intensity,

patient age, co-existing disease, potential drug interactions,

prior treatment history, physician preference, patient pref-

erence, and route of administration. The idea that some

Table 3 Drugs used to treat opioid-induced side effects

Drug (brand name) Dose (mg/kg)

(<50 kg)

Dose (mg)

(>50 kg)

Interval (h) Daily maximum

dose (mg/kg)

(<50 kg)

Daily maximum

dose (mg)

(>50 kg)

Comments

Senna (Senokot�)

(Perdiem�)

10 187–364 Give at

bedtime

Up to 2 regular

strength tablets

Up to 8 regular

strength

tablets

Syrup: 218 mg/5 ml

Tablet: 187 mg

X-strength tablet: 364 mg

Stool bulk; Best

administered with full

glass of water, milk, or

fruit juice

Docusate (Colace�)

(Dulcolax�)

10 50–500 mg/

day in 1–4

doses

6 40 500 Best administered with full

glass of water, milk, or

fruit juice

Diphenhydramine

(Benadryl�)

1 50 4–6 50 50 Very sedating

Useful for both nausea

and vomiting, and pruritus

Serotonin 5 HT-3

receptor antagonist

NA NA Used for nausea and

vomiting

(Zofran �) 0.15 4 4–6

(Dolasetron �) 0.35 12.5 4–6

Neurocrit Care (2009) 10:387–402 395

opioids are ‘‘weak’’ (e.g., codeine) and others are ‘‘strong’’

(e.g., morphine) is outdated. All are capable of treating pain

regardless of its intensity if the dose is adjusted appropri-

ately. For the most part, at equipotent doses, opioids have

similar effects and side effects, particularly where respira-

tory depression is concerned. Characteristics of selected lopioid agonist drugs are listed for quick reference in

Table 2.

The use of meperidine requires some additional dis-

cussion. An entire generation of physicians believes that

meperidine causes less respiratory depression and less

biliary spasm than morphine. This was based on a study of

postoperative adult patients in which half received 10 mg

morphine and the other half 10 mg of meperidine. The

meperidine group had less respiratory depression and bil-

iary spasm than morphine. They also had more pain. The

equianalgesic dose of meperidine is 100 mg. When the

study was repeated with appropriate dosing the investiga-

tors found that meperidine had the same side effect profile

as morphine [69]. Meperidine has a neurotoxic metabolite,

normeperidine, that possesses no analgesic properties and

relies on the kidney for its excretion. Normeperidine

accumulation causes CNS excitation, resulting in a range of

toxic reactions from anxiety and tremors to grand mal

seizures.

Commonly Used Intravenous Opioids

Intravenous opioids are the primary drugs used in the treat-

ment of moderate to severe pain. Morphine (from Morpheus,

the Greek God of Sleep) is the gold standard for analgesia

against which all other opioids are compared. When small

doses, 0.1 mg/kg (i.v., i.m., s.c.), are administered to other-

wise unmedicated patients in pain, analgesia usually occurs

without loss of consciousness. The relief of tension, anxiety,

and pain usually may result in drowsiness and sleep as well.

Once steady-state pharmaco*kinetics are achieved, morphine

has a duration of action that is approximately 3–4 h. Fentanyl

is a shorter acting alternative which has become a favored

analgesic for intraoperative anesthesia, and can also be used

for patient-controlled analgesia (PCA) and breakthrough

pain. Fentanyl is approximately 100 (50–100) times more

potent than morphine (the equianalgesic dose is 0.001 mg/

kg) and is largely devoid of hypnotic or sedative activity.

Finally, methadone is increasingly being used for post-

operative pain relief and for the treatment of intractable

pain. Primarily thought of as a drug to treat or wean opioid-

addicted or -dependent patients, methadone’s long half-life

of elimination and high oral bioavailability provides very

long duration of effective analgesia (Table 2). Addition-

ally, methadone is unique in that it is also an NMDA

receptor antagonist which makes it useful for treatment of

chronic and neuropathic pain and may prevent opioid-

induced hyperalgesia.

Commonly Used Oral Opioids

Codeine, oxycodone (the opioid in Tylox� and Percocet�)

and hydrocodone (the opioid in Vicodin� and Lortab�) are

opioids which are frequently used to treat pain in children

and adults, particularly for less severe pain or when

patients are being converted from parenteral opioids to

enteral ones (Table 2). Oral morphine is commonly used in

regimens for chronic pain (e.g., cancer). Codeine, oxyco-

done, and hydrocodone are most commonly administered

in the oral form, usually in combination with acetamino-

phen or aspirin [70].

In equipotent doses, codeine, oxycodone, hydrocodone,

and morphine are equal both as analgesics and respiratory

depressants (Table 2). In addition, they share with other

opioids common effects on the central nervous system

including sedation, respiratory depression, and nausea

through stimulation of the chemoreceptor trigger zone in

the brain stem. This last attribute of the opioids is partic-

ularly true for codeine. There are many fewer problems

with nausea and vomiting with oxycodone. Codeine,

hydrocodone, and oxycodone have a bioavailability of

approximately 60% following oral ingestion. The analgesic

effects occur as early as 20 min following ingestion and

reach a maximum at 60–120 min. The plasma half-life of

elimination is 2.5–4 h.

Codeine is the most popularly prescribed enteral and

parenteral opioid in neurosurgical practice and is fre-

quently administered intramuscularly [1]. Although it is an

effective analgesic when administered parenterally, intra-

muscular codeine has no advantage over morphine or any

other opioid. If it has any use (and we do not think it does),

it is as an oral analgesic. Codeine undergoes nearly com-

plete metabolism in the liver prior to its final excretion in

urine. Approximately 10% of codeine is metabolized into

morphine (cytochrome P450 2D6) and it is this 10% that is

responsible for codeine’s analgesic effect. Interestingly,

approximately 10% of the population are ‘‘slow’’ metabo-

lizers of codeine into morphine and, in these patients,

codeine will have little analgesic effect. Additionally, 10%

of the population are ‘‘rapid’’ metabolizers in whom a

‘‘standard’’ dose may produce excessive sedation and

respiratory depression.

Like oxycodone, codeine, and hydrocodone, morphine is

also very effective when given orally, but only about 20–

30% of an oral dose of morphine reaches the systemic

circulation. In the past, this led many to conclude that

morphine was ineffective when administered orally. In

fact, this was the result of failing to provide sufficient

396 Neurocrit Care (2009) 10:387–402

morphine. Therefore, when converting a patient’s intrave-

nous morphine requirement to oral maintenance, one must

multiply the intravenous dose by 3–4.

Whereas oral morphine is prescribed alone, oral codeine,

hydrocodone, and oxycodone are usually prescribed in

combination with either acetaminophen or aspirin (Tyle-

nol� and codeine elixir, Percocet�, Tylox�, Vicodin�,

Lortab�). Acetaminophen and aspirin potentiate the anal-

gesia produced by opioids, and permit satisfactory analgesia

with less opioid. Typically, codeine is prescribed in a dose

of 0.5–1 mg/kg. As stated previously, in all ‘‘combination

preparations’’, beware of inadvertently administering an

hepatotoxic acetaminophen dose when increasing opioid

doses for uncontrolled pain [71]. Acetaminophen toxicity

may result from a single toxic dose, from repeated ingestion

of large doses of acetaminophen (e.g., in adults, 7.5–10 g

daily for 1–2 days, children 60–420 mg/kg/day for

1–2 days) or from chronic ingestion. Codeine elixirs are

available in virtually every pharmacy and contain 120 mg

acetaminophen and 12 mg codeine per teaspoon (5 ml) [70].

Codeine and acetaminophen are also available as ‘‘num-

bered’’ tablets, e.g., Tylenol� number 1, 2, 3, or 4. The

number refers to how much codeine is in each tablet.

Tylenol� number 4 has 60 mg codeine, number 3 has

30 mg, number 2 has 15 mg, and number 1 has 7.5 mg.

Hydrocodone is prescribed in a dose of 0.05–0.1 mg/kg.

The elixir is available as 2.5 mg/5 ml combined with

acetaminophen 167 mg/5 ml. As a tablet, it is available in

hydrocodone doses between 2.5 and 10 mg, combined with

500–650 mg acetaminophen. Oxycodone is prescribed in a

dose of 0.05–0.1 mg/kg. Unfortunately, the elixir is not

available in most pharmacies. When it is, it comes either as

1 mg/ml or 20 mg/ml. This can obviously result in cata-

strophic dispensing errors. In tablet form, oxycodone is

commonly available as a 5 mg tablet or as Tylox� (500 mg

acetaminophen and 5 mg oxycodone) or Percocet�

(325 mg acetaminophen and 5 mg oxycodone).

Oxycodone is also available without acetaminophen in a

sustained-release tablet for use in chronic pain. Like many

other time-release tablets, it must not be crushed and

therefore cannot be administered through a gastric tube

since breaking the tablet results in the immediate release of

an extremely large amount of oxycodone. Like sustained-

release morphine (see below), sustained-release oxycodone

is intended only for use in opioid-tolerant patients with

chronic pain, and not for routine postoperative pain. Fur-

thermore, in patients with rapid GI transit, sustained-

release preparations may not be absorbed at all (liquid

methadone may be an alternative).

Oral morphine is available as a liquid in various con-

centrations (as much as 20 mg/ml), a tablet (such as MSIR,

for ‘‘morphine sulfate immediate release’’; available in 15

and 30 mg tablets), and as a sustained-release preparation

(MSContin and Oramorph tablets, and Kadian ‘‘sprinkle

capsules,’’ which may be opened and sprinkled on apple-

sauce). Because it is so concentrated, the liquid is

particularly easy to administer to severely debilitated

patients. Indeed, in terminal patients who cannot swallow,

liquid morphine will provide analgesia when simply

dropped into the patient’s mouth [70].

Pain Management Adjuvants

Several drugs that are used in chronic and sympathetically

mediated pain are increasingly being used in the multi-

modal management of acute pain. Apart from their ability

to limit opioid-induced hyperalgesia as described earlier

[39], gabapentin and pregabalin, when given preopera-

tively, have been shown to decrease postoperative pain and

opioid consumption in many surgical procedures [72].

Whether this family of drugs may be useful in patients

undergoing intracranial surgery or provides better opioid

sparing and/or improved pain relief is presently unknown.

As indicated above, the a2-agonist dexmedetomidine is

being used for sedation during ‘‘awake’’ craniotomy and in

the intensive care unit [47]. The resulting adrenergic

modulation of spinal cord activity [73] can reduce sub-

sequent pain and opioid consumption [48]. Clonidine,

which is often administered to reduce hypertension, is also

an a2-agonist with similar analgesic properties [74].

However, because of their sedative nature, the a2-agonists

are unlikely to be used primarily for their analgesic effects

when intracranial surgery is the focus. The NMDA antag-

onists ketamine and dextromethorphan are analgesics with

significant preemptive analgesic effects [30, 75, 76] whose

use can also limit opioid-induced hyperalgesia [38]. The

dissociative nature of ketamine may render it less desirable

for use in association with intracranial surgery, and dex-

tromethorphan can produce sedation and other types of

CNS symptoms. Tramadol is a nonopioid analgesic which,

in contrast to the drugs already described in this section,

has actually been evaluated as an analgesic in association

with intracranial surgery and is, therefore, described in

more detail below.

Tramadol is a synthetic 4-phenyl-piperidine analog of

codeine, is a centrally acting synthetic analgesic that has

been used for 30 years in Europe and was approved by the

FDA for adult use in the U.S. in 1995 [77, 78] It is a

racemic mixture of two enantiomers, (+)-tramadol and

(-)-tramadol [78, 79]. The (+)-enantiomer has a moderate

affinity for the l-opioid receptor, greater than that of the

(-)-enantiomer. In addition, the (+)-enantiomer inhibits

serotonin uptake and the (-)-enantiomer blocks the reup-

take of norepinephrine, complementary properties which

result in a synergistic antinociceptive interaction between

Neurocrit Care (2009) 10:387–402 397

the two enantiomers. Tramadol may also produce analgesia

as an a2-agonist [80]. A metabolite (O-desmethyltramadol)

binds to opioid receptors with a greater affinity than the

parent compound and could contribute to tramadol’s

analgesic effects as well. However, in most animal tests

and human clinical trials, the analgesic effect of tramadol is

only partially blocked by the opioid antagonist naloxone,

suggesting an important nonopioid mechanism as well.

Tramadol’s intravenous analgesic effect has been

reported to be 10–15 times less than that of morphine and is

roughly equianalgesic with NSAIDs [78, 81]. Unlike

NSAIDs and opioid-mixed agonist/antagonists (e.g.,

butorphanol, nalbuphine), the therapeutic use of tramadol

has not been associated with clinically important side

effects such as respiratory depression, constipation, or

sedation. In addition, analgesic tolerance has not been a

serious problem during repeated administration, and nei-

ther psychological dependence nor euphoric effects are

observed in long-term clinical trials. Thus, tramadol may

offer significant advantages in the management of pain

following intracranial surgery by virtue of its dual mech-

anism of action, its lack of a ceiling effect, and its minimal

respiratory depression. Tramadol may be administered

orally, rectally, or intravenously [82, 83]. Oral and intra-

venous tramadol is administered in doses of 1–2 mg/kg;

the higher dose provides a longer duration of action with-

out increasing side effects.

Complications and Side Effects

Regardless of the method of administration, all opioids

commonly produce unwanted side effects, such as pruritus,

nausea and vomiting, constipation, urinary retention, cog-

nitive impairment, tolerance, and dependence [84]. The most

common in patients with both acute and chronic opioid

administration is bowel dysfunction. Opioid-induced bowel

dysfunction (OBD), often described as constipation in

patients taking opioids chronically and as postoperative ileus

in patients taking opioids acutely, is virtually universal [85,

86]. Historically, opioids were used to treat diarrhea prior to

their use as analgesics. Many patients suffer needlessly from

pain because they would rather suffer than experience these

opioid-induced side effects [87], and because physicians are

reluctant to prescribe opioids because of these common side

effects and because of their fear of respiratory depression.

Rather than reacting to side effects, we recommend that

anticipatory best practice treatment protocols and algo-

rithms be put into practice at the initiation of opioid

therapy. These protocols outlined in Fig. 3 and Table 3 are

used in our practice. For example, all patients being treated

with opioids, even for short periods of time, will become

constipated and should be treated with senna or other stool

bulking and softeners at the initiation of therapy. Further,

several clinical and laboratory studies have demonstrated

that low-dose naloxone infusions (0.25–1 mcg/kg/h) can

prophylactically treat or prevent opioid-induced side

effects without affecting the quality of analgesia or opioid

requirements [88]. This was confirmed in a study in chil-

dren and adolescents, and our institution now routinely

initiates a simultaneous low-dose naloxone infusion

whenever PCA is initiated in children [89]. Finally, a

peripheral opioid antagonist, methylnaltrexone (Relistor�),

has recently been approved by the United States Food and

Drug Administration and may dramatically alter how we

deal with unwanted opioid-induced side effects, particu-

larly OBD.

Additional Considerations

Clearly, patients presenting for intracranial surgery are far

from uniform with respect to age, mental capacity, and

underlying comorbidities. Pediatric, elderly, and critically

ill or injured patients can all differ in their ability to par-

ticipate in pain assessment and the pharmaco*kinetics and

pharmacodynamics underlying their response to analgesics.

Extremes of age, prior or acquired cognitive limitations, and

language barriers can interfere with pain assessment and,

therefore, analgesic therapy. Since, most pharmaco*kinetic

studies are performed in healthy adult volunteers, those with

limited illness or those with stable chronic disease, these

data are of limited use in patients at extremes of age or those

who are critically ill. These sources of variability can be

offset by careful titration of analgesics, something that is

possible only if pain can be adequately assessed.

Analgesic therapy in pediatric patients often requires pain

assessment tools different from the discrete 0–10 scale so

useful with cognitively intact adults, and is further burdened

by lingering beliefs that some groups of pediatric patients do

not experience pain despite almost two decades of data

demonstrating the contrary [90, 91]. Pain assessment in

pediatric populations is still possible with appropriate pain

assessment tools, the use of which will make clear the

capacity of these patients to experience pain. These include

additional tools that permit self-report (e.g., cartoon images

or colors that represent different pain levels) as well as

observational scales based on physiologic variables (e.g.,

heart rate and blood pressure) and behavioral criteria (e.g.,

posture and grimacing) [91, 92]. These tools may be useful

for any age group where cognitive impairment or language

barriers could interfere with the assessment of pain. Unique

pharmaco*kinetic considerations, if any, and specific dosing

regimens for pediatric patients are given above and in the

associated tables for each of the analgesics discussed.

However, even for patients without conditions that could

398 Neurocrit Care (2009) 10:387–402

alter pharmaco*kinetics, pain assessment and analgesic

titration are essential. Interestingly, patient-controlled anal-

gesic administration can be used safely and effectively by

relatively young patients or their proxies (e.g., family

member or nurse) [93].

In elderly patients, analgesic therapy is complicated by

differing analgesic requirements, preexisting and postop-

erative cognitive decline, and altered pharmaco*kinetics. In

this population, perioperative pain assessment may be more

difficult due to preexisting or acquired cognitive decline,

situations for which observational pain assessment tools

have been developed [94]. For reasons yet to be elucidated,

elderly patients often perceive acute pain to a lesser extent

than younger patients [95, 96], and this is consistent with

what has been observed following intracranial surgery [18].

Postoperative delirium is often observed in elderly patients

[97], is more likely to occur in those with preexisting

cognitive decline, may be exacerbated by opioids, and may

also be exacerbated by the pain and stress associated with

surgery, perhaps through activation of the glucocorticoid

system [98, 99]. The increased proportion of adipose tissue

in elderly patients can alter the volume of distribution of

the opioids and other analgesics, and decreases in hepatic

and renal function can affect their elimination [100].

Analgesic therapy in critically ill patients is fraught with

constraints. Analgesic therapy may exacerbate hemody-

namic instability or even contribute to it through histamine

release when morphine is administered more than a few

milligrams at a time. Individual alterations in renal or

hepatic function must be considered. The opioids interfere

with normal sleep architecture [101, 102] and are though to

play the major roll in the decline of restorative sleep known

to occur postoperatively [103]. This probably contributes to

the disrupted sleep experienced by patients in intensive

care settings [104], but opioids should not be withheld

because untreated pain can also disrupt normal sleep pat-

terns [105].

Analgesic Therapy Following Intracranial Surgery—

Current Practice

A recent survey revealed that intramuscular codeine phos-

phate is still the primary analgesic in the majority (70%) of

centers [36]. Only 13% used morphine as the primary anal-

gesic. Only 4% used PCA. Thus, not only does the traditional

teaching regarding the minimal nature of perioperative pain

following intracranial surgery persist [1], so does the tradi-

tional teaching regarding its management.

Although it now clear that better analgesic therapy is

required following intracranial surgery, the available litera-

ture on how to accomplish this remains sparse. Certainly, for

supratentorial craniotomy using a propofol–remifentanil

anesthetic, acetaminophen alone is inadequate [106], but

when combined with tramadol or nalbuphine administered

on an ‘‘as needed’’ (PRN) basis both combinations were

equally effective, resulting in mild pain for the first 24

postoperative hours. Several studies have compared intra-

muscular codeine phosphate with morphine sulfate. When

intramuscular morphine sulfate PRN is compared to intra-

muscular codeine phosphate PRN, morphine was found to be

equally safe with a more sustained period of effectiveness

[107]. When intramuscular codeine was compared with PCA

morphine administration, there was a slight reduction in pain

in the PCA group without any differences in side effects or

adverse events [108]. Intramuscular codeine phosphate was

also compared with intramuscular tramadol, each adminis-

tered at the conclusion of surgery, with minimal differences

in analgesic effects, but greater side effects in the tramadol

group [109]. Oxycodone was administered by PCA to

patients following supratentorial craniotomy who received

either paracetamol or ketoprofen (an NSAID), with few

differences observed and no adverse events related to opioid

administration [110]. A recent study sought to demonstrate

the safety and efficacy of PCA opioid administration fol-

lowing supratentorial craniotomy [111]. Following a

balanced anesthetic technique with fentanyl and a preinci-

sional scalp block with bupivacaine, patients were

randomized to receive fentanyl either PRN or via PCA.

Patients in the PCA group used significantly more fentanyl

and achieved significantly better pain control. Nonetheless,

sedation scores and respiratory parameters were identical

between the two groups. Collectively, these studies indicate

that opioid administration by PCA following supratentorial

craniotomy is safe and effective.

Scalp block and local anesthetic infiltration tailored to

the given surgical approach can be an important adjunct to

a balanced anesthetic technique by reducing intraoperative

anesthetic requirements, and can also reduce perioperative

pain. When the incision site is infiltrated with a long-acting

local anesthetic such as bupivacaine 0.25% some intraop-

erative hemodynamic responses were blunted and pain in

the immediate postoperative period was reduced [24].

When a scalp block (Fig. 1) is performed with a long-

acting local anesthetic prior to supratentorial craniotomy,

pain throughout the first postoperative day is reduced [18,

23]. Some of this reduction in pain is likely due to a pre-

emptive analgesic effect [30].

Recommendations

The authors currently embrace a multimodal approach that

combines the benefits of a balanced anesthetic technique

with fentanyl, nitrous oxide, and a volatile anesthetic with a

scalp block using bupivacaine 0.5% and placed prior to

Neurocrit Care (2009) 10:387–402 399

surgery. If no prior scalp incision has been made, then

the scalp block is supplemented by the surgeons with

bupivacaine 0.25% at the incision site. Postoperatively, all

patients receive acetaminophen at regular intervals

(650 mg pr, while initially NPO then 1 g PO q 6 h in an

adult). Care is taken to avoid oral opioids in combination

with acetaminophen due to the potential for prescribing

potentially toxic doses [18]. Patients typically receive

fentanyl via PCA with no background infusions, a bolus

dose of 0.25–0.50 lg/kg with a lockout of 6 min and up to

10 boluses per hour. If only PRN opiate administration is

permitted, then fentanyl 25–50 lg iv q 10 min is suggested

for adults. On the first postoperative day patients transition

to oral analgesics which include, along with the acetami-

nophen, oxycodone 5–10 mg q 3–4 h in an adult.

Conclusions

Future studies will be required to determine whether the

amount of opioid necessary to keep patients undergoing

posterior fossa procedures comfortable can be safely

administered by PCA. It would also be beneficial to know

whether adjuncts such as gabapentin should be administered

prior to craniotomy as is done with other types of surgery

[112]. Overall, analgesic therapy for intracranial surgery

now stands on a new foundation with data demonstrating

the necessity of treating pain in these patients and that, in

contrast to traditional teaching, safe and effective analgesic

therapy is possible with drugs and techniques commonly

used to treat the pain associated with other types of surgical

procedures.

References

1. Stoneham MD, Walters FJ. Post-operative analgesia for crani-

otomy patients: current attitudes among neuroanaesthetists. Eur

J Anaesthesiol. 1995;12(6):571–5.

2. Cold GE, Felding M. Even small doses of morphine might

provoke ‘‘luxury perfusion’’ in the postoperative period after

craniotomy. Neurosurgery. 1993;32(2):327.

3. Breivik H, Borchgrevink PC, Allen SM, et al. Assessment of

pain. Br J Anaesth. 2008;101(1):17–24.

4. Grossman SA, Sheidler VR, Swedeen K, Mucenski J, Piantadosi

S. Correlation of patient and caregiver ratings of cancer pain.

J Pain Symptom Manage. 1991;6(2):53–7.

5. Berkow LC, Erdek M, Gottschalk A, Thompson RE, White ED,

Yaster M. Pain assessment in adult post-craniotomy patients: a

preliminary prospective study. Anesth Analg. 2005;100:S-248.

6. Eich E, Reeves JL, Jaeger B, Graff-Radford SB. Memory for

pain: relation between past and present pain intensity. Pain.

1985;23(4):375–80.

7. Hunter M, Philips C, Rachman S. Memory for pain. Pain.

1979;6(1):35–46.

8. Juhl IU, Christensen BV, Bulow HH, Wilbek H, Dreijer NC,

Egelund B. Postoperative pain relief, from the patients’ and the

nurses’ point of view. Acta Anaesthesiol Scand. 1993;37(4):

404–9.

9. Svensson I, Sjostrom B, Haljamae H. Influence of expectations

and actual pain experiences on satisfaction with postoperative

pain management. Eur J Pain. 2001;5(2):125–33.

10. Dawson R, Spross JA, Jablonski ES, Hoyer DR, Sellers DE,

Solomon MZ. Probing the paradox of patients’ satisfaction with

inadequate pain management. J Pain Symptom Manage. 2002;

23(3):211–20.

11. Durieux ME, Himmelseher S. Pain control after craniotomy: off

balance on the tightrope? J Neurosurg. 2007;106:207–9.

12. De Benedittis G, Lorenzetti A, Migliore M, Spagnoli D, Tiberio

F, Villani RM. Postoperative pain in neurosurgery: a pilot study

in brain surgery. Neurosurgery. 1996;38(3):466–9.

13. Quiney N, Cooper R, Stoneham M, Walters F. Pain after cra-

niotomy. A time for reappraisal? Br J Neurosurg. 1996;10(3):

295–9.

14. Talke PO, Gelb AW. Postcraniotomy pain remains a real

headache! Eur J Anaesthesiol. 2005;22:324–6.

15. de Gray LC, Matta BF. Acute and chronic pain following cra-

niotomy: a review. Anaesthesia. 2005;60(7):693–704.

16. Dunbar PJ, Visco E, Lam AM. Craniotomy procedures are

associated with less analgesic requirements than other surgical

procedures. Anesth Analg. 1999;88(2):335–40.

17. Klimek M, Ubben JF, Ammann J, Borner U, Klein J, Verbrugge

SJ. Pain in neurosurgically treated patients: a prospective

observational study. J Neurosurg. 2006;104(3):350–9.

18. Gottschalk A, Berkow LC, Stevens RD, et al. A prospective

evaluation of pain and analgesic use following major elective

intra-cranial surgery. J Neurosurg. 2007;106:210–6.

19. Thibault M, Girard F, Moumdjian R, Chouinard P, Boudreault

D, Ruel M. Craniotomy site influences postoperative pain fol-

lowing neurosurgical procedures: a retrospective study. Can J

Anaesth. 2007;54(7):544–8.

20. Irefin SA, Schubert A, Bloomfield EL, DeBoer GE, Mascha EJ,

Ebrahim ZY. The effect of craniotomy location on postoperative

pain and nausea. J Anesth. 2003;17(4):227–31.

21. Koperer H, Deinsberger W, Jodicke A, Boker DK. Postoperative

headache after the lateral suboccipital approach: craniotomy

versus craniectomy. Minim Invasive Neurosurg. 1999;42(4):

175–8.

22. Schessel DA, Nedzelski JM, Rowed D, Feghali JG. Pain after

surgery for acoustic neuroma. Otolaryngol Head Neck Surg.

1992;107(3):424–9.

23. Nguyen A, Girard F, Boudreault D, et al. Scalp nerve blocks

decrease the severity of pain after craniotomy. Anesth Analg.

2001;93(5):1272–6.

24. Bloomfield EL, Schubert A, Secic M, Barnett G, Shutway F,

Ebrahim ZY. The influence of scalp infiltration with bupivacaine

on hemodynamics and postoperative pain in adult patients

undergoing craniotomy. Anesth Analg. 1998;87(3):579–82.

25. Leslie K, Troedel S, Irwin K, et al. Quality of recovery from

anesthesia in neurosurgical patients. Anesthesiology. 2003;99(5):

1158–65.

26. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery.

A review of predictive factors. Anesthesiology. 2000;93(4):

1123–33.

27. Kaur A, Selwa L, Fromes G, Ross DA. Persistent headache after

supratentorial craniotomy. Neurosurgery. 2000;47(3):633–6.

28. Hanson MB, Glassco*ck MEIII, Brandes JL, Jackson CG. Med-

ical treatment of headache after suboccipital acoustic tumor

removal. Laryngoscope. 1998;108(8 Pt 1):1111–4.

29. Ryzenman JM, Pensak ML, Tew JM Jr. Headache: a quality of

life analysis in a cohort of 1,657 patients undergoing acoustic

neuroma surgery, results from the acoustic neuroma association.

Laryngoscope. 2005;115(4):703–11.

400 Neurocrit Care (2009) 10:387–402

30. Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of

preemptive analgesia for acute postoperative pain management:

a meta-analysis. Anesth Analg. 2005;100(3):757–73.

31. Gray’s Anatomy. 37th ed. Edinburgh: Churchill Livingstone;

1989. p. 1129.

32. Feindel W, Penfield W, McNaughton F. The tentorial nerves and

localization of intracranial pain in man. Neurology. 1960;10:

555–63.

33. Cavallotti D, Artico M, De SS, Iannetti G, Cavallotti C. Cate-

cholaminergic innervation of the human dura mater involved in

headache. Headache. 1998;38(5):352–5.

34. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain:

risk factors and prevention. Lancet. 2006;367(9522):1618–25.

35. Swenson JD, Davis JJ, Johnson KB. Postoperative care of the

chronic opioid-consuming patient. Anesthesiol Clin North

America. 2005;23(1):37–48.

36. Roberts GC. Post-craniotomy analgesia: current practices in

British neurosurgical centres—a survey of post-craniotomy

analgesic practices. Eur J Anaesthesiol. 2005;22(5):328–32.

37. Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative

systematic review. Anesthesiology. 2006;104(3):570–87.

38. Celerier E, Rivat C, Jun Y, et al. Long-lasting hyperalgesia

induced by fentanyl in rats: preventive effect of ketamine.

Anesthesiology. 2000;92(2):465–72.

39. Van Elstraete AC, Sitbon P, Mazoit JX, Benhamou D. Gaba-

pentin prevents delayed and long-lasting hyperalgesia induced

by fentanyl in rats. Anesthesiology. 2008;108(3):484–94.

40. Gelb AW, Salevsky F, Chung F, et al. Remifentanil with mor-

phine transitional analgesia shortens neurological recovery

compared to fentanyl for supratentorial craniotomy. Can J

Anaesth. 2003;50(9):946–52.

41. Guy J, Hindman BJ, Baker KZ, et al. Comparison of remifentanil

and fentanyl in patients undergoing craniotomy for supratentorial

space-occupying lesions. Anesthesiology. 1997;86(3):514–24.

42. Gerlach K, Uhlig T, Huppe M, et al. Remifentanil-propofol versus

sufentanil-propofol anaesthesia for supratentorial craniotomy: a

randomized trial. Eur J Anaesthesiol. 2003;20(10): 813–20.

43. Hopf HW. Is it time to retire high-concentration nitrous oxide?

Anesthesiology. 2007;107(2):200–1.

44. Mathews DM, Gaba V, Zaku B, Neuman GG. Can remifentanil

replace nitrous oxide during anesthesia for ambulatory orthope-

dic surgery with desflurane and fentanyl? Anesth Analg. 2008;

106(1):101–8.

45. Petersen-Felix S, Luginbuhl M, Schnider TW, Curatolo M,

Rendt-Nielsen L, Zbinden AM. Comparison of the analgesic

potency of xenon and nitrous oxide in humans evaluated by

experimental pain. Br J Anaesth. 1998;81(5):742–7.

46. Georgiev SK, Kohno T, Ikoma M, Yamakura T, Baba H. Nitrous

oxide inhibits glutamatergic transmission in spinal dorsal horn

neurons. Pain. 2008;134(1–2):24–31.

47. Cormack JR, Orme RM, Costello TG. The role of alpha2-ago-

nists in neurosurgery. J Clin Neurosci. 2005;12(4):375–8.

48. Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN,

Ozcan B. Intraoperative infusion of dexmedetomidine reduces

perioperative analgesic requirements. Can J Anaesth. 2006;53

(7):646–52.

49. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six

interventions for the prevention of postoperative nausea and

vomiting. N Engl J Med. 2004;350(24):2441–51.

50. Yaksh TL, Dirig DM, Conway CM, Svensson C, Luo ZD,

Isakson PC. The acute antihyperalgesic action of nonsteroidal,

anti-inflammatory drugs and release of spinal prostaglandin E2

is mediated by the inhibition of constitutive spinal cyclooxy-

genase-2 (COX-2) but not COX-1. J Neurosci. 2001;21(16):

5847–53.

51. Harner SG, Beatty CW, Ebersold MJ. Impact of cranioplasty on

headache after acoustic neuroma removal. Neurosurgery.

1995;36(6):1097–9.

52. Ruckenstein MJ, Harris JP, Cueva RA, Prioleau G, Alksne J.

Pain subsequent to resection of acoustic neuromas via suboc-

cipital and translabyrinthine approaches. Am J Otol. 1996;17(4):

620–4.

53. van Leeuwen JP, Braspenning JC, Meijer H, Cremers CW.

Quality of life after acoustic neuroma surgery. Ann Otol Rhinol

Laryngol. 1996;105(6):423–30.

54. Gottschalk A, Ochroch EA. Is preemptive analgesia clinically

effective? In: Fleisher L, editor. Evidence-based practice of

anesthesia. Philadelphia: Saunders; 2008.

55. Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia II: recent

advances and current trends [L’analgesie preventive II : progres

recents et nouvelle orientation]. Can J Anaesth. 2001;48(11):

1091–101.

56. Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia I: physio-

logical pathways and pharmacological modalities. Can J Anaesth.

2001;48(10):1000–10.

57. Abram SE, Yaksh TL. Morphine, but not inhalation anesthesia,

blocks post-injury facilitation. The role of preemptive suppression

of afferent transmission. Anesthesiology. 1993;78(4):713–21.

58. Yaster M. Non-steroidal antiinflammatory drugs. In: Yaster M,

Krane EJ, Kaplan RF, Cote CJ, Lappe DG, editors. Pediatric

pain management and sedation handbook. St. Louis: Mosby

Year Book, Inc; 1997. p. 19–28.

59. Murat I, Baujard C, Foussat C, et al. Tolerance and analgesic

efficacy of a new i.v. paracetamol solution in children after

inguinal hernia repair. Paediatr Anaesth. 2005;15(8):663–70.

60. Cashman JN. The mechanisms of action of NSAIDs in analge-

sia. Drugs. 1996;52 Suppl 5:13–23.

61. Vane JR, Botting RM. Mechanism of action of aspirin-like

drugs. Semin Arthritis Rheum. 1997;26(6 Suppl 1):2–10.

62. Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-

inflammatory drugs. Am J Med. 1998;104(3A):2S–8S. discus-

sion 21S–2.

63. Jouzeau JY, Terlain B, Abid A, Nedelec E, Netter P. Cyclo-

oxygenase isoenzymes. How recent findings affect thinking

about nonsteroidal anti-inflammatory drugs. Drugs. 1997;53(4):

563–82.

64. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2.

Annu Rev Pharmacol Toxicol. 1998;38:97–120.

65. Levesque LE, Brophy JM, Zhang B. The risk for myocardial

infarction with cyclooxygenase-2 inhibitors: a population study

of elderly adults. Ann Intern Med. 2005;142(7):481–9.

66. Johnsen SP, Larsson H, Tarone RE, et al. Risk of hospitalization

for myocardial infarction among users of rofecoxib, celecoxib,

and other NSAIDs: a population-based case-control study. Arch

Intern Med. 2005;165(9):978–84.

67. Snyder SH, Pasternak GW. Historical review: opioid receptors.

Trends Pharmacol Sci. 2003;24(4):198–205.

68. Standifer KM, Pasternak GW. G proteins and opioid receptor-

mediated signalling. Cell Signal. 1997;9(3–4):237–48.

69. Radnay PA, Duncalf D, Novakovic M, Lesser ML. Common

bile duct pressure changes after fentanyl, morphine, meperi-

dine, butorphanol, and naloxone. Anesth Analg. 1984;63(4):

441–4.

70. Krane EJ, Yaster M, Yaster M. Transition to less invasive

therapy. In: Yaster M, Krane EJ, Kaplan RF, Cote CJ, Lappe

DG, editors. Pediatric pain management and sedation handbook.

St. Louis: Mosby Year Book, Inc; 1997. p. 147–62.

71. Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misad-

ventures with acetaminophen: hepatoxicity after multiple doses

in children [see comments]. J Pediatr. 1998;132(1):22–7.

Neurocrit Care (2009) 10:387–402 401

72. Gilron I. Gabapentin and pregabalin for chronic neuropathic and

early postsurgical pain: current evidence and future directions.

Curr Opin Anaesthesiol. 2007;20(5):456–72.

73. Pertovaara A. Antinociception induced by alpha-2-adrenoceptor

agonists, with special emphasis on medetomidine studies. Prog

Neurobiol. 1993;40(6):691–709.

74. Boyd RE. Alpha2-adrenergic receptor agonists as analgesics.

Curr Top Med Chem. 2001;1(3):193–7.

75. Himmelseher S, Durieux ME. Ketamine for perioperative pain

management. Anesthesiology. 2005;102(1):211–20.

76. Siu A, Drachtman R. Dextromethorphan: a review of N-methyl-

D-aspartate receptor antagonist in the management of pain. CNS

Drug Rev. 2007;13(1):96–106.

77. Minto CF, Power I. New opioid analgesics: an update. Int

Anesthesiol Clin. 1997;35(2):49–65.

78. Raffa RB. A novel approach to the pharmacology of analgesics.

Am J Med. 1996;101(1A):40S–46S.

79. Raffa RB, Friderichs E, Reimann W, et al. Complementary and

synergistic antinociceptive interaction between the enantiomers

of tramadol. J Pharmacol Exp Ther. 1993;267(1):331–40.

80. Desmeules JA, Piguet V, Collart L, Dayer P. Contribution of

monoaminergic modulation to the analgesic effect of tramadol.

Br J Clin Pharmacol. 1996;41(1):7–12.

81. Naguib M, Seraj M, Attia M, Samarkandi AH, Seet M, Jaroudi

R. Perioperative antinociceptive effects of tramadol. A pro-

spective, randomized, double-blind comparison with morphine.

Can J Anaesth. 1998;45(12):1168–75.

82. Bozkurt P. Use of tramadol in children. Paediatr Anaesth.

2005;15(12):1041–7.

83. Gunes Y, Gunduz M, Unlugenc H, Ozalevli M, Ozcengiz D.

Comparison of caudal vs intravenous tramadol administered

either preoperatively or postoperatively for pain relief in boys.

Paediatr Anaesth. 2004;14(4):324–8.

84. Yaster M, Kost-Byerly S, Maxwell LG. Opiod agonists and

antagonists. In: Schechter NL, Berde CB, Yaster M, editors.

Pain in infants, children, and adolescents. Philadelphia: Lip-

pincott Williams and Wilkins; 2003. p. 181–224.

85. Fallon MT, Hanks GW. Morphine, constipation and perfor-

mance status in advanced cancer patients. Palliat Med. 1999;

13(2):159–60.

86. Glare P, Lickiss JN. Unrecognized constipation in patients with

advanced cancer: a recipe for therapeutic disaster. J Pain

Symptom Manage. 1992;7(6):369–71.

87. Watcha MF, White PF. Postoperative nausea and vomiting. Its

etiology treatment, and prevention. Anesthesiology. 1992;77(1):

162–84.

88. Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R.

Opioid-sparing effects of a low-dose infusion of naloxone in

patient-administered morphine sulfate. Anesthesiology.

1997;87(5):1075–81.

89. Maxwell LG, Kaufmann SC, Bitzer S, et al. The effects of a

small-dose naloxone infusion on opioid-induced side effects and

analgesia in children and adolescents treated with intravenous

patient-controlled analgesia: a double-blind, prospective, ran-

domized, controlled study. Anesth Analg. 2005;100(4):953–8.

90. Maxwell LG, Yaster M. Perioperative management issues in

pediatric patients. Anesthesiol Clin North America. 2000;18(3):

601–32.

91. American Academy of Pediatrics. Committee on Psychosocial

Aspects of Child and Family Health; Task Force on Pain in

Infants, Children, and Adolescents. The assessment and man-

agement of acute pain in infants, children, and adolescents.

Pediatrics. 2001;108(3):793–7.

92. McGrath PA. An assessment of children’s pain: a review of

behavioral, physiological and direct scaling techniques. Pain.

1987;31(2):147–76.

93. Monitto CL, Greenberg RS, Kost-Byerly S, et al. The safety and

efficacy of parent-/nurse-controlled analgesia in patients less

than six years of age. Anesth Analg. 2000;91(3):573–9.

94. Murdoch J, Larsen D. Assessing pain in cognitively impaired

older adults. Nurs Stand. 2004;18(38):33–9.

95. Li SF, Greenwald PW, Gennis P, Bijur PE, Gallagher EJ. Effect

of age on acute pain perception of a standardized stimulus in the

emergency department. Ann Emerg Med. 2001;38(6):644–7.

96. Gagliese L, Katz J. Age differences in postoperative pain are scale

dependent: a comparison of measures of pain intensity and quality

in younger and older surgical patients. Pain. 2003;103(1–2):

11–20.

97. Bryson GL, Wyand A. Evidence-based clinical update: general

anesthesia and the risk of delirium and postoperative cognitive

dysfunction. Can J Anaesth. 2006;53(7):669–77.

98. Gaudreau JD, Gagnon P. Psychotogenic drugs and delirium

pathogenesis: the central role of the thalamus. Med Hypotheses.

2005;64(3):471–5.

99. Brown TM. Drug-induced delirium. Semin Clin Neuropsychia-

try. 2000;5(2):113–24.

100. ElDesoky ES. Pharmaco*kinetic-pharmacodynamic crisis in the

elderly. Am J Ther. 2007;14(5):488–98.

101. Dimsdale JE, Norman D, DeJardin D, Wallace MS. The effect of

opioids on sleep architecture. J Clin Sleep Med. 2007;3(1):33–6.

102. Shaw IR, Lavigne G, Mayer P, Choiniere M. Acute intravenous

administration of morphine perturbs sleep architecture in heal-

thy pain-free young adults: a preliminary study. Sleep. 2005;28

(6):677–82.

103. Knill RL, Moote CA, Skinner MI, Rose EA. Anesthesia with

abdominal surgery leads to intense REM sleep during the first

postoperative week. Anesthesiology. 1990;73(1):52–61.

104. Friese RS, Az-Arrastia R, McBride D, Frankel H, Gentilello

LM. Quantity and quality of sleep in the surgical intensive care

unit: are our patients sleeping? J Trauma. 2007;63(6):1210–4.

105. Onen SH, Onen F, Courpron P, Dubray C. How pain and

analgesics disturb sleep. Clin J Pain. 2005;21(5):422–31.

106. Verchere E, Grenier B, Mesli A, Siao D, Sesay M, Maurette P.

Postoperative pain management after supratentorial craniotomy.

J Neurosurg Anesthesiol. 2002;14(2):96–101.

107. Goldsack C, Scuplak SM, Smith M. A double-blind comparison

of codeine and morphine for postoperative analgesia following

intracranial surgery. Anaesthesia. 1996;51(11):1029–32.

108. Stoneham MD, Cooper R, Quiney NF, Walters FJ. Pain following

craniotomy: a preliminary study comparing PCA morphine with

intramuscular codeine phosphate. Anaesthesia. 1996;51(12):

1176–8.

109. Jeffrey HM, Charlton P, Mellor DJ, Moss E, Vucevic M.

Analgesia after intracranial surgery: a double-blind, prospective

comparison of codeine and tramadol. Br J Anaesth. 1999;83(2):

245–9.

110. Tanskanen P, Kytta J, Randell T. Patient-controlled analgesia

with oxycodone in the treatment of postcraniotomy pain. Acta

Anaesthesiol Scand. 1999;43(1):42–5.

111. Morad A, Winters BD, Yaster M, et al. Intravenous patient

controlled analgesia safely and effectively treats pain after

supratentorial intracranial surgery: a prospective randomized

controlled trial. J Neurosurg. 2008; Accepted for publication.

112. Mathiesen O, Moiniche S, Dahl JB. Gabapentin and postoper-

ative pain: a qualitative and quantitative systematic review, with

focus on procedure. BMC Anesthesiol. 2007;7:6.

402 Neurocrit Care (2009) 10:387–402

(PDF) The Perioperative Management of Pain from Intracranial Surgery - DOKUMEN.TIPS (2024)

FAQs

What are the consequences of postoperative pain? ›

Inadequate treatment of acute postoperative pain can lead to further complications, such as respiratory tract infections, psychological symptoms, deep vein thrombosis, and chronic pain.

Keep Reading ›

What are the effects of poorly managed pain? ›

The problems of insomnia, depression, suicide, attention deficit, memory loss, and cognitive deficiencies are extremely common in persistent pain patients.

Get More Info Here ›

What are opioid analgesics after surgery? ›

Opioid Analgesia

The most commonly used intravenous opioids for postoperative pain are morphine, hydromorphone (dilaudid), and fentanyl. Morphine is the standard choice for opiates and is widely used.

Find Out More ›

How can perioperative pain be managed? ›

For many patients, although not all, simple analgesia, including Panadol and non-steroidal anti-inflammatory medicines, should be the mainstay for discharge analgesia.

When is post-op pain the worst? ›

Generally speaking, post-surgical pain is at its worst for the first 24 to 48 hours after a procedure. 9 This can vary depending on several factors, including how well your pain is being controlled. Nonsteroidal anti-inflammatory drugs (NSAIDs) like Motrin (ibuprofen) are typically used for 10 days or fewer.

View Details ›

What is the most appropriate medication to manage postoperative pain? ›

In most cases after surgery, oral (PO), intramuscular (IM), or intravenous (IV) opioids will be prescribed. Doctors usually prefer to prescribe oral opioid medications for use when you return home.

Read On ›

How do you tolerate surgery pain? ›

Over-the-counter medications, such as acetaminophen and ibuprofen, work very well for minor surgeries and laparoscopic ones. For bigger procedures—such as joint replacements, spine surgery or cardiac surgeries—opioid medications might be needed. Patients who need surgery for broken bones may also need opioids.

Get More Info Here ›

What is used to reduce pain during surgery? ›

For some patients, the anesthesiologist may recommend using a combination of drugs and techniques that can include a nerve block, general anesthesia—and, in some cases, a small amount of opioid medication—to provide the most effective relief in a particular situation.

Read On ›

What is the most common postoperative complication? ›

The most common complications include:

Shock. Shock is a severe drop in blood pressure that causes a dangerous slowing of blood flow throughout the body. ...
Bleeding. ...
Wound infection. ...
Deep vein thrombosis. ...
Pulmonary embolism. ...
Lung problems. ...
Urinary retention. ...
Reaction to anesthesia.

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What are the side effects of postoperative complications? ›

Complications may include:

Shock. ...
Hemorrhage. ...
Wound infection. ...
Deep vein thrombosis (DVT) and pulmonary embolism (PE). ...
Pulmonary embolism. ...
Lung (pulmonary) complications. ...
Urinary retention. ...
Reaction to anesthesia.

Read On ›

What is a risk factor for postoperative pain? ›

Materials and methods: The interdisciplinary pain team identified 7 potential risk factors that may lead to inadequate pain control postoperatively including (1) history of physical, emotional, or sexual abuse; (2) history of anxiety; (3) history of drug or alcohol abuse; (4) preoperative nonsteroidal anti-inflammatory ...

What are the consequences of acute pain? ›

Untreated acute pain has the potential to produce acute neurohumoral changes, neuronal remodeling, and long-lasting psychologic and emotional distress and may lead to prolonged chronic pain states.

(PDF) The Perioperative Management of Pain from Intracranial Surgery - DOKUMEN.TIPS (2024)

FAQs

What are the consequences of postoperative pain? ›

When is post-op pain the worst? ›