ANAESTHESIA AND ANALGESIA: CONTRIBUTION TO SURGERY,
Department of Anaesthesia, Christchurch School of Medicine, University of Otago, Christchurch, New Zealand
Anaesthetists provide comprehensive perioperative medical care to patients undergoing surgical and diagnostic procedures, includingpostoperative intensive care when needed. They are involved in the management of perioperative acute pain as well as chronic pain.
This manuscript considers some of the recent advances in modern anaesthesia and their contribution to surgery, from the basicmechanisms of action, to the delivery systems for general and regional anaesthesia, to the use of new drugs and new methods ofmonitoring. It assesses the resulting progress in acute and chronic pain services and looks at patient safety and risk management.
It speculates on directions that may shape its future contributions to the management of the patient undergoing surgery.
Key words: anaesthesia, analgesia, contribution to surgery.
Abbreviations: AEP, auditory-evoked potentials; COX-2, cyclo-oxgenase 2; CSA, continuous spinal anaesthesia; CSE,
combined spinal and epidural; EEG, electroencephalograph; GABAA, gamma-aminobutyric acid-A; PONV, postoperativenausea and vomiting; TCI, target-controlled infusion; TOE, transoesophageal echocardiography.
William Morton first publicly showed inhalational anaesthesia in
How do anaesthetics work? Despite the widespread presence of
1846 with the use of diethyl ether. At the end of the nineteenth
clinical anaesthesiology in surgical practice, the mechanisms by
century, August Bier discovered that a class of drugs (local anaes-
which diverse inhalational agents give general anaesthesia remain
thetics) could stop neural transmission. Since those humble begin-
unknown. There are complex multisite, multilevel (molecular,
nings, the application of anaesthesia and analgesia has advanced
subcellular, cellular, local microcircuit) interactions.1 Binding
rapidly particularly in the past 50 years, making surgery much
sites for general anaesthetics have been identified on several
safer and allowing more sophisticated surgery to take place. The
ion channels, including the nicotinic acetylcholine and gamma-
explosion hazard with anaesthetic gases was largely conquered
aminobutyric acid-A (GABAA) receptors.2 At clinically effective
with the development of the halogenated agents in the 1950s.
concentrations, a broad variety of general anaesthetics increase
Introduction of sevoflurane and desflurane during the last decades
apparent GABA sensitivity and prolong inhibitory post-synaptic
offered new perspectives to clinical anaesthesia, characterized by
current mediated by GABAA receptors. Advancement in mol-
rapid onset of and recovery from anaesthesia.
ecular techniques has allowed greater understanding of the action
Anaesthetists provide comprehensive perioperative medical
of anaesthetic agents through the use of the ‘knock-in’ mice
care to patients undergoing surgical and diagnostic procedures,
model.3 Conception of the mechanisms of action of many drugs
including postoperative intensive care when needed. They are
routinely given in the operating room can be improved by the use
involved in the management of perioperative acute pain as well
of protein biomarker technology (such as protein microarray
as chronic pain. This manuscript considers some of the recent
chips).4 A greater understanding of the mechanisms of anaesthe-
advances in modern anaesthesia and their contributions to the
sia will allow the development of more selective anaesthetics to
management of the surgical patient. They range from the ‘basic
achieve maximal clinical efficacy with minimal adverse effects.
mechanisms of action’, the delivery systems for general andregional anaesthesia, the use of new drugs to the new methodsof monitoring. The resulting progress in acute perioperative and
chronic pain services is assessed in addition to patient safety and
Regional anaesthesia provides a substitute for general anaesthe-
risk management. It speculates on directions that may shape any
sia. Alternatively, it can be used to supplement general anaesthe-
sia and provide postoperative analgesia. There is continuousdevelopment and refinement of regional anaesthetic techniquesfor various types of surgery, as well as for continuous regional
E. Shipton DM, FANZCA, FFPMANZCA; A. Lin MBChB.
analgesia.5 The quality of blockade and analgesia depends on
Correspondence: Professor Edward Shipton, Department of Anaesthesia,
accurate administration of local anaesthetic around the intended
Christchurch School of Medicine, University of Otago, PO Box 4345, Christ-
nerve structures. The use of nerve stimulation and insulated
needles plus the development of ultrasound guidance (with an
accurate depiction of the underlying anatomy) allows for
Accepted for publication 15 October 2007.
precise needle placement.6 Ultrasound helps monitor the real-time
Ó 2008 The AuthorsJournal compilation Ó 2008 Royal Australasian College of Surgeons
administration of local anaesthetics or analgesics.6 Ultrasound or
New drugs in clinical and research development in anaes-
even computed tomography-guided nerve block techniques are
particularly useful when the underlying anatomy is complex.7–10
Regional anaesthesia precludes the disadvantages seen with
general anaesthesia (intubation, long recovery, postoperative nau-
sea and vomiting (PONV), impaired oxygenation and depressed
ventilation), It has been successfully used in the fields of obstet-
rics and in lower-extremity, cardiothoracic,11–13 breast 14 and
laparoscopic surgeries.15 The risks of anaesthetic and surgical
complications are not any higher with regional anaesthesia than
with general anaesthesia.14 However, it is not without its risks,
including drug adverse effects, such as cardiovascular toxicity and
Combining the use of spinal and epidural techniques (CSE) has
been gaining popularity over recent years.16 It provides rapid
onset of anaesthesia without increasing the complications.17
Recent evidence shows that lower doses provide adequate anal-
gesia while reducing the incidence of motor block.18,19 The spinal
needle can be used as a guide for the advancement of epidural
needle and prevent the epidural catheter from puncturing the
dura.20 A lower incidence of unintentional ‘wet tap’ has been
shown with this technique. Fetal/neonatal bradycardia is occa-
sionally seen with CSE technique, but is not associated with
increased rates of emergency caesarean sections.21
In elderly and frail patients, in whom general or epidural anaes-
thesia may be too risky,22 continuous spinal anaesthesia (CSA) has
recently regained popularity.23 CSA offers haemodynamic stability,
as hypotension is less likely with CSA when compared with
CSE.24,25 However, with any neuraxial administration, hypotension
and haematoma formation remain concerns that deserve further
attention and research.24 In neuraxial opioid analgesia, opioid phys-
icochemical properties determine efficacy and safety. Intrathecal
morphine, fentanyl and sufentanil are most commonly used.26 Other
analgesic adjuvants include clonidine, dexmedetomidine and adren-aline, all working through a
-adrenergic receptors.26 Other agents inthe early stages of investigation for neuraxial analgesia include neo-
stigmine, ketamine, midazolam, adenosine and ziconotide.26
The availability of the stereoisomer of ketamine with its increasedpotency and lower incidence of psychomimetic adverse effects in
equianalgesic doses (compared with the racemate) has increased
The quest for safety has long been a central part of the search for
its non-anaesthetic use as an adjunct analgesic.31
new anaesthetic/analgesic agents. Recent fields examined includethe inert gases, the racaemic mixtures (ketamine, ropivacaine,
levobupivacaine), the coxibs and the cyclodextrins (Table 1).
Provided there are no contraindications, the use of the cyclo-oxgenase 2 (COX-2) inhibitors (the coxibs) preoperatively show
clear benefits in terms of reduced postoperative pain, analgesicconsumption and patient satisfaction.32 With their chronic use,
Of all the inert gases, only xenon has considerable anaesthetic
peptic ulceration remains a reduced but significant adverse
properties under normobaric conditions.27 Xenon’s anaesthetic
effect.33 Their lack of antiplatelet effects is important in patients
effect is possibly achieved through the non-competitive antagonism
on anticoagulants and in neuraxial blockade.33 COX-2 inhibitors
of N-methyl-D-aspartate receptor.25 It is highly lipid soluble with
may not produce bronchospasm (at analgesic doses), but may have
a very low blood/gas partition coefficient (0.14)28 that makes induc-
similar adverse effects as general non-steroidal anti-inflammatory
tion of and emergence from anaesthesia more rapid compared with
drugs on renal function.33 More trials are needed to determine
other inhalational anaesthetic agents.27 Xenon has also been shown
their possible prothrombotic effect.
to possess cardioprotective and neuroprotective effects.29,30 It mayprove beneficial in patients at high risk for neurological or cardiac
damage during surgery. With the advancement in anaesthetic deliv-ery systems, the cost–benefit of using xenon gas may in future
With regard to local anaesthetics, the main focus has been on the
justify its use in high-risk surgical patients.
development of the enantiomer-specific compounds, ropivacaine
Ó 2008 The AuthorsJournal compilation Ó 2008 Royal Australasian College of Surgeons
and levobupivacaine. These provide similar efficacy to bupiva-
ation of tumour and certain neurodegenerative disease proteins.54
caine in peripheral and central nerve blockade, but with reduced
Local anaesthetics in turn have been shown to have potent anti-
risk of severe cardiotoxicity.34 Human studies have borne this out
inflammatory properties.54 Some of the new synthetic opioids are
with levobupivacaine having fewer effects than bupivacaine on
devoid of immunosuppressive functions seen with morphine.55
QRS prolongation, central nervous system symptoms and electro-
There remains a need to examine how genetic diversity or
acquired defects alter the immune response to tissue injury and
There has been no effective antidote for toxic doses of local
infection.53 This will improve risk stratification and create pos-
anaesthetics. Recently, intralipid was shown to effectively reverse
local anaesthetic toxicity in the animal model by hastening theloss of bupivacaine from cardiac tissue.35,36 Several human case
reports using a bolus of 20% intralipid followed by an intralipidinfusion show promising efficacy.37,38 As other effective alterna-
Progress in computing technology has allowed the development
tives have not been found, the use of intralipid is worth consid-
of target-controlled infusion (TCI) devices, with drugs delivered
ering in the management of local anaesthetic toxicity.39
to achieve specific predicted target blood drug concentrations.56A set of pharmacokinetic parameters is selected using computer
simulation of a known infusion scheme. The selected model isincorporated into a computer-compatible infusion pump. Clinical
Adenosine-1 receptors play a role in antinociception in the spinal
trials with such systems provide appropriate target concentra-
cord.40 The direct administration of adenosine reduces the amount
tions.56 TCI allows for the administration of small doses of
of intraoperative volatile anaesthetic required and contributes to
short-acting anaesthetic drugs, such as opioids (remifentanil and
postoperative pain relief.41 An additional advantage of adenosine
fentanyl) and propofol.57 The use of TCI has been extended to
is its cardioprotective effect, making it an attractive future option
include paediatric anaesthesia and sedation.
as part of a balanced anaesthetic technique.42
Continuous electronic physiological monitoring is core to the safe
Over the past decades, the search for short termination of action of
delivery of anaesthesia during surgery. Devices are being devel-
non-depolarizing muscle relaxants has continued. Sugammadex
oped that can assess depth of sedation and anaesthesia, stroke
(Org 25969) is a cyclodextrin.43 It forms a tight complex with
volume, cardiac output, systemic vascular resistance, cerebral
aminosteroid-based non-depolarizing muscle relaxants (rocuro-
haemodynamic and metabolic variables.58 Some new ventilators
nium, pancuronium, vecuronium). Animal and human studies
are capable of monitoring lung mechanics and of automatically
show a rapid dose-dependent decrease in the concentration of free
adjusting the ventilator settings to prevent ventilator associated
and bound non-depolarizing muscle relaxants.44,45 It is devoid of
lung injury or to aid weaning.58 New monitors include cerebral
the cardiovascular side-effects associated with acetylcholinester-
microdialysis to provide online analysis of tissue biochemistry.58
ase inhibitors such as neostigmine. Continued research is required
Novel imaging methods include positron emission tomography
to clarify the role of sugammadex before this termination tech-
and functional magnetic resonance imaging.58
nique can replace the standard use of succinylcholine for short-term muscle relaxation.46
Non-invasive monitoring is increasingly being developed for use inanaesthesia. For example, the use of continuous cerebral oximetry
Anaesthetic agents interact with the underlying pathological
protects against the risk of intraoperative cerebral ischaemia.59 Aor-
mechanisms of ischaemia reperfusion injury and protect the myo-
tic blood flow can be determined with the use of non-invasive
cardium by a preconditioning mechanism.47 Volatile anaesthetics
oesophageal echo-Doppler monitoring.60 Thoracic bioimpedance
activate ATP-sensitive potassium channels (similar to ischaemia-
has been used as well to investigate haemodynamic changes.61
induced preconditioning) thereby providing a cardioprotectiveeffect.48–50 Preconditioning by volatile anaesthetics involves the
activation of protein kinase C and mitogen-activated proteinkinases. Transcription factors are activated, resulting in the induc-
Over the past 10 years, depth of anaesthesia monitoring has
tion of specific genes in the heart.51 The effects are most evident
emerged to aid anaesthetists by the development of processed elec-
when the volatile agent is given throughout the entire procedure.52
troencephalographic methods, such as bispectral index, mid-latency
The anaesthetist may therefore substantially influence the critical
auditory-evoked potentials (AEP), and spectral entropy.62–64 These
situation of ischaemia-reperfusion during surgery by choosing the
correlate well to clinical observed level of consciousness.62–64 These
monitoring techniques improve the titration of both inhaled andi.v. anaesthetic agents by avoiding excessive anaesthesia and aware-ness, promoting faster emergence from anaesthesia, and managing
Knowledge of the host immune response to anaesthesia/analgesia
Auditory evoked potentials form an electrical manifestation of
and surgery needs to be integrated with the role of immunity in
the brain response to an auditory stimulus. Mid-latency auditory
general in the progression of many of the chronic diseases.53
evoked potentials as well as the coherent frequency of the auditory
Volatile anaesthetics appear to suppress effector functions of both
evoked potential are useful for monitoring depth of anaesthesia.66
the innate and adaptive immunity and may facilitate the prolifer-
It is possible to acquire and process raw electroencephalograph
Journal compilation Ó 2008 Royal Australasian College of Surgeons
(EEG) and frontal electromyogram signals and produce two spec-
tral entropy-based indices (namely response entropy and state
Postoperative nausea and vomiting remains problematic to every
entropy).67 The M-Entropy module provides useful information
anaesthetist and surgeon. There is strong evidence that volatile
on the cortical state of the patient during general anaesthesia. It
anaesthetics (like opioids) are emetogenic with no meaningful
acts as an indirect measure of the adequacy of analgesia.68 With the
differences between halothane, enflurane, isoflurane, sevoflurane
use of these new monitoring technologies, closed loop anaesthesia
and desflurane.78 Various anti-emetic strategies are associated
in the true sense has finally emerged.
with a reduction rate of approximately 25–30%.79 However, whena propofol technique is substituted for a volatile anaesthetic tech-
nique, the risk for PONV is reduced by approximately one-fifth.78
In closed or rebreathing circuits, fresh gas supply matches uptake.
Interestingly, all anti-emetics (dexamethasone, droperidol and
A lower fresh gas flow rate is therefore used. Humidity and tem-
ondansetron) work independently, so a combination benefit can
perature are conserved. In recent years, new computer-assisted
be derived.80 If PONV is a serious problem, general anaesthesia
control of gas delivery has dramatically improved the gas com-
can be avoided by using a regional, opioid-free anaesthetic
position in closed circuits. Fast gas analysers and appropriate
algorithms regulate the exact amount of volatile and fresh gasinjected into the system. This minimizes the difference between
the actual volatile gas concentration and vaporizer setting seen inthe traditional closed loop low-flow system. Closed loop systems
Anaesthesia was one of the first medical professions to treat
are able to reach and maintain a preset target.69 The computer
patient safety as an independent problem. Preoperative evaluation
program takes over the role of dose administration while the
carried out by anaesthetists aims primarily to estimate the risk of
anaesthetist only enters the desirable level to be maintained.
perioperative complications and to create opportunities to opti-
Closed-loop feedback allows the realization of ‘quantitative
mize the patient’s condition before surgery.81 Patient safety is
closed-system anaesthesia’ in the operating room.70,71
primarily determined by quality of systems of care. There has
To monitor muscle relaxation, a closed-loop muscle relaxation
been steady progress in anaesthesia safety because of the devel-
system can be formed by the connection of a muscle relaxation
opment of performance standards, an increase in error reporting,
monitor (TOF Watch SX; Organon Schering-Plough, Kenilworth,
integration of information technology and improved safety sys-
NJ, USA) to a laptop computer.72 A controller algorithm pro-
tems.82 This has led to a 10-fold reduction in anaesthesia-related
gramme then communicates with a syringe pump.72
deaths over the past few decades, despite the increase in more
The linking of EEG monitoring to TCI for closed loop anaes-
challenging operations and the number of older and sicker
thesia remains a research tool. Nunes et al. recently developed
patients. According to the Institute of Medicine’s 1999 report
a fuzzy relational classifier that uses AEP features to classify the
entitled To err is human, ‘.
anesthesiology has successfully
depth of anaesthesia.73 It is a machine-learning model based on
reduced anesthesia mortality rates from two deaths per 10 000
fuzzy clustering and fuzzy relationship that somehow mimics
anesthetics administered, to one death per 200 000 to 300 000
In addition to fibre-optic airway devices, supraglottic airway devi-ces have revolutionized airway management in anaesthesia over
The occurrence of postoperative pain remains problematic. In
the last 15 years. Examples include the classic, intubating and
2003, Apfelbaum found that 80% of patients still experience post-
Proseal (LMA North America, Inc., San Diego, CA, USA) laryn-
operative pain.84 Acute pain management services first entered
geal mask airway, the Combitube (Tyco-Kendall, Mansfield, MA,
clinical practice in the late 1980s.85 Anaesthetists have played
USA), the laryngeal tube, and laryngeal tube sonda mark I and II.74
an important role in this interdisciplinary approach to managing
The Glidescope (Verathon Inc., Bothell, WA, USA) is a new vid-
postoperative pain.86 Evidence of earlier discharge with the use of
eolaryngoscope.75 It has a digital camera incorporated in its blade
an acute pain service has been shown.87,88
that displays a view of the vocal cords on a monitor. This allows
Inadequately relieved postoperative pain leads to complica-
visual placement of a tracheal tube. Improved designs include the
tions, such as deep vein thrombosis, lung infections and myocar-
paediatric ProSeal–Laryngeal mask airway76 and the Microcuff
dial ischaemia, which may extend hospital stay.89 New analgesics
(Kimberly-Clark Health Care, Roswell, GA, USA) paediatric endo-
and analgesic drug delivery systems are being developed. For
example, the use of i.v. paracetamol avoids absorption and bio-availability variability and produces more predictable plasma par-acetamol concentrations than the oral route.90 Nitroxyparacetamol
(or nitroacetaminophen) is a new, potent nitric oxide-releasing
Transoesophageal echocardiography (TOE) has proved useful to
version of paracetamol that has analgesic and anti-inflammatory
anaesthetists in guiding therapy in haemodynamically unstable
properties.33,91 It should prove a useful analgesic for patients with
patients in the operating room and intensive care unit. TOE provides
paracetamol-induced liver damage. The anticonvulsant gabapen-
real-time dynamic information about the anatomy and physiology
tin has shown analgesic efficacy in several surgical procedures,
of the whole heart.77 It is of value in the management of patients
particularly to reduce post-surgical neuropathic pain.92 Early
undergoing procedures (including cardiac valvular repair), in sur-
studies with its successor, pregabalin are in progress.
gery for endocarditis and in surgery of the thoracic aorta. It con-
Advances in neurobiology and clinical medicine have estab-
tributes useful information in a wide range of cardiac pathologies.77
lished that the fetus and newborn may experience acute and even
Ó 2008 The AuthorsJournal compilation Ó 2008 Royal Australasian College of Surgeons
chronic pain.93 Many scales have been developed in an attempt to
standardize pain measurement in neonates.93 Recently, attention
How could anaesthetists aid the patient undergoing surgery in
has been paid to the short-term and long-term outcomes of pre-
future? Software could be developed to integrate patient monitor-
mature infants and newborns exposed to noxious stimuli. These
ing and response to anaesthesia and surgery, resulting in an early
include simple heel prick, invasive intubation and surgery.
warning system that alerts the anaesthetist to impending disas-
Repeated or prolonged painful experiences are linked to deleteri-
ter.107 New techniques like nanotechnology could enable precise
ous outcomes in preterm neonates.93 It could alter the develop-
timing and site of drug delivery.107 Delivery systems under devel-
ment of the nervous system and lead to abnormal pain behaviour
opment could deposit drugs at the desired site of action, control
in later life.94,95 This shows the importance of good analgesia
their rate of release, and to neutralize overdose, bind and elimin-
ate previously given drugs.107 Emerging applications could bedeveloped by pharmacogenomic research as well. In post-surgicalpain medicine, Anaesthetists could make use of new molecular
targets, such as sodium channel blockers (Nav 1.3, Nav 1.7 andNav 1.8) 108; potassium channel openers in sensory neurons109;
Anaesthetists often lead the medical specialist team involved in
N-type calcium channels (Cav 2.2) blockers109; P2X4 and
chronic pain management. In some patients, the hyperphenomena
P2X7 receptor antagonists in microglia110; vanilloid receptor-1
(primary and secondary hyperalgesia, mechanical allodynia) that
antagonists111,112; and the cannabinoid-2 receptor agonists.111,113
are normal in the first days or weeks after surgery, do not regress,but persist beyond the usual course of an acute surgical injury.96Acute persistent pain soon becomes chronic pain.96 Chronic pain
demands a greater use of the health resources and has proved to be
Anaesthesia historically grew out of surgery and the two disci-
a major public health burden.97 Unrelieved postoperative pain and
plines continue to work in close partnership. Anaesthetists and
severe perioperative pain have been shown to be risk factors for
surgeons form an integrated team linking together to do their
the development of chronic pain.98 This emphasizes the need for
utmost for the good of the patient. This relationship plays an
effective perioperative pain management.
important role in enabling patient safety and avoiding errors. Of
There has been tremendous progress in pain medicine (parti-
importance to the surgeon are the recent developments in anaes-
cularly interventional pain medicine) enhancing the contribution
thetic technology and the advances in drugs and monitoring
of the anaesthetist in managing post-surgical pain syndromes.
methods. As illustrated in this manuscript, these developments
Advances in neuroimaging techniques (positron emission tomog-
have accelerated and altered the work carried out in the operating
raphy, functional magnetic resonance imaging) help identify brain
room. In addition, evidence is just beginning to emerge on the
mechanisms for more effective treatments for chronic pain. Rapid
relation between specific anaesthetics and anaesthetic techniques
progress is being made towards the development of gene ther-
and long-term clinical outcomes after surgery.114
apy.80 For example, viral vector-mediated gene transfer achievesfocal production of short-lived analgesic peptides (or growth fac-tors). This prevents disc degeneration and promotes chondrocyte
and disc regeneration.99 This should soon have clinical applica-
1. Urban BW. Current assessment of targets and theories of anaes-
tion for both the anaesthetist and the surgeon involved in pain
thesia. Br. J. Anaesth. 2002; 89: 167–83.
2. Clark M. Sensitivity of the rat hippocampal GABA (A) receptor
New techniques in neuromodulation have promoted existing
alpha 4 subunit to electroshock seizures. Neurosci. Lett. 1998;
teamwork between the anaesthetist and the surgeon. The reduced
demand for health-care resources by patients receiving neuromo-
3. Jurd R, Arras M, Lambert S et al. General anesthetic actions in
dulation (peripheral nerve stimulation, spinal cord stimulation)
vivo strongly attenuated by a point mutation in the GABA(A)
suggests substantial long-term economic benefits in patients with
receptor beta3 subunit. FASEB J. 2003; 17: 250–52.
neuropathic pain and chronic refractory angina receiving these.100
4. Atkins JH, Johansson JS. Technologies to shape the future:
Anaesthetists may aid the orthopaedic surgeons by the radiofre-
proteomics applications in anesthesiology and critical care
quency heating of annular tears, leading to an improvement in the
medicine. Anesth. Analg. 2006; 102: 1207–16.
5. Rosenberg PH. Future of regional anaesthesia. Acta Anaesthe-
pain of internal disc disruption.101 In addition they can help out by
carrying out kyphoplasty, a minimally invasive technique that
6. Marhofer P, Greher M, Kapral S. Ultrasound guidance in
appears to improve both pain and function in patients with verte-
regional anaesthesia. Br. J. Anaesth. 2005; 94: 7–17.
bral fractures because of osteoporosis.102
7. De Cicco M, Matovic M, Bortolussi R et al. Celiac plexus
New analgesic delivery systems are being developed for anaes-
block: injectate spread and pain relief in patients with regional
thetists to assist surgeons in perioperative pain relief. Progress is
anatomic distortions. Anesthesiology 2001; 94: 561–5.
being made in the ability to combine local anaesthetics with lip-
8. Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus
osomes (bupivacaine, morphine) and polymer microspheres.103
block for treatment of cancer pain: a meta-analysis. Anesth.
Systems designed to transiently circumvent the barrier function
of the stratum corneum, using iontophoresis and sonophoresis,
9. Schneider-Kolsky ME, Pike J, Connell DA. CT-guided suprascap-
ular nerve blocks: a pilot study. Skeletal Radiol. 2004; 33: 277–82.
will expand the range of drugs that can be delivered transder-
10. Shanahan EM, Smith MD, Wetherall M et al. Suprascapular
mally.91 New analgesic drugs are being studied as well to treat
nerve block in chronic shoulder pain: are the radiologists better?
post-surgical neuropathic pain. These include pregabalin, a novel
Ann. Rheum. Dis. 2004; 63: 1035–40.
alpha (2)-delta ligand104; ziconotide, a drug derived from a snail
11. Hemmerling TM, Noiseux N, Basile F, Noel MF, Prieto I.
toxin that works on the calcium channels105 and endocannabi-
Awake cardiac surgery using a novel anesthetic technique.
noids, that naturally suppress nociceptive neurotransmission.106
Can. J. Anaesth. 2005; 52: 1088–92.
Journal compilation Ó 2008 Royal Australasian College of Surgeons
12. Kessler P, Neidhart G, Bremerich DH et al. High thoracic epi-
32. Straube S, Derry S, McQuay HJ, Moore RA. Effect of preoper-
dural anesthesia for coronary artery bypass grafting using two
ative Cox-II-selective NSAIDs (coxibs) on postoperative out-
different surgical approaches in conscious patients. Anesth.
comes: a systematic review of randomized studies. Acta
Anaesthesiol. Scand. 2005; 49: 601–13.
13. Kirali K, Kocak T, Guzelmeric F, Goksedef D, Kayalar N,
33. Power I. Recent advances in postoperative pain therapy. Br. J.
Yakut C. Off-pump awake coronary revascularization using
bilateral internal thoracic arteries. Ann. Thorac. Surg. 2004;
34. Van de Velde M, Dreelinck R, Dubois J. Determination of the
full dose-response relation of intrathecal bupivacaine, levobu-
14. Singh AP, Tewari M, Singh DK, Shukla HS. Cervical epidural
pivacaine, and ropivacaine, combined with sufentanil, for labor
anesthesia: a safe alternative to general anesthesia for patients
analgesia. Anesthesiology 2007; 106: 149–56.
undergoing cancer breast surgery. World J. Surg. 2006; 30:
35. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emul-
sion infusion rescues dogs from bupivacaine-induced cardiac
15. Kruschinski D, Homburg S. Lift-(gasless) laparoscopic surgery
toxicity. Reg. Anesth. Pain Med. 2003; 28: 198–202.
under regional anesthesia. Surg. Technol. Int. 2005; 14: 193–6.
36. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro
16. Burnstein R, Buckland R, Pickett JA. A survey of epidural
MF, Cwik MJ. Pretreatment or resuscitation with a lipid infu-
analgesia for labour in the United Kingdom. Anaesthesia
sion shifts the dose-response to bupivacaine-induced asystole in
rats. Anesthesiology 1998; 88: 1071–5.
17. Hughes D, Simmons SW, Brown J, Cyna AM. Combined spinal-
37. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of
epidural versus epidural analgesia in labour. Cochrane Data-
a patient with ropivacaine-induced asystole after axillary plexus
block using lipid infusion. Anaesthesia 2006; 61: 800–801.
18. Lee BB, Ngan Kee WD, Hung VY, Wong EL. Combined spinal-
38. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft
epidural analgesia in labour: comparison of two doses of intrathe-
JB. Successful use of a 20% lipid emulsion to resuscitate
cal bupivacaine with fentanyl. Br. J. Anaesth. 1999; 83: 868–71.
a patient after a presumed bupivacaine-related cardiac arrest.
19. Parpaglioni R, Frigo MG, Sebastiani M et al. High volume
of subarachnoid levobupivacaine decreases drug requirement
39. Picard J, Meek T. Lipid emulsion to treat overdose of local
in first stage labor analgesia. Minerva Anestesiol. 2004; 70:
anaesthetic: the gift of the glob. Anaesthesia 2006; 61: 107–9.
40. Sawynok J. Adenosine receptor activation and nociception.
20. Norris MC, Grieco WM, Borkowski M et al. Complications of
Eur. J. Pharmacol. 1998; 347: 1–11.
labor analgesia: epidural versus combined spinal epidural tech-
41. Hayashida M, Fukunaga A, Fukuda K. The characteristics of
niques. Anesth. Analg. 1994; 79: 529–37.
intravenous adenosine-induced antinociception in a rabbit
21. Albright GA, Forster RM. Does combined spinal-epidural anal-
model of acute nociceptive pain: a comparative study with remi-
gesia with subarachnoid sufentanil increase the incidence of
fentanil. Anesth. Analg. 2006; 103: 1004–10.
emergency cesarean delivery? Reg. Anesth. 1997; 22: 400–405.
42. Willems L, Ashton KJ, Headrick JP. Adenosine-mediated car-
22. Michaloudis D, Petrou A, Bakos P et al. Continuous spinal
dioprotection in the aging myocardium. Cardiovasc. Res. 2005;
anesthesia/analgesia for the perioperative management of
high-risk patients. Eur. J. Anaesthesiol. 2000; 18: 239–47.
43. Adam JM, Bennett DJ, Bom A et al. Cyclodextrin-derived host
23. Denny NM, Harrop-Griffiths W. Location, location, location!
molecules as reversal agents for the neuromuscular blocker
Ultrasound imaging in regional anaesthesia. Br. J. Anaesth.
rocuronium bromide: synthesis and structure-activity relation-
ships. J. Med. Chem. 2002; 45: 1806–16.
24. Klimscha W, Weinstabl C, Ilias W et al. Continuous spinal
44. De Boer HD, van Egmond J, van de Pol F, Bom A, Booij LH.
anesthesia with a microcatheter and low-dose bupivacaine
Reversal of profound rocuronium neuromuscular blockade by
decreases the hemodynamic effects of centroneuraxis blocks
sugammadex in anesthetized rhesus monkeys. Anesthesiology
in elderly patients. Anesth. Analg. 1993; 77: 275–80.
25. Labaille T, Benhamou D, Westermann J. Hemodynamic effects
45. Sorgenfrei IF, Norrild K, Larsen PB et al. Reversal of rocuro-
of continuous spinal anesthesia: a comparative study between
nium-induced neuromuscular block by the selective relaxant
low and high doses of bupivacaine. Reg. Anesth. 1992; 17:
binding agent sugammadex: a dose-finding and safety study.
26. Schug SA, Saunders D, Kurowski I, Paech MJ. Neuraxial drug
46. Kopman AF. Sugammadex: a revolutionary approach to neuro-
administration. CNS Drugs 2006; 20: 917–33.
muscular antagonism. Anesthesiology 2006; 104: 631–3.
27. Rasmussen LS, Schmehl W, Jakobsson J. Comparison of
47. Weber NC, Preckel B, Schlack W. The effect of anaesthetics on
xenon with propofol for supplementary general anaesthesia
the myocardium–new insights into myocardial protection. Eur.
for knee replacement: a randomized study. Br. J. Anaesth. 2006;
J. Anaesthesiol. 2005; 22: 647–57.
48. Conzen PF, Fischer S, Detter C, Peter K. Sevoflurane provides
28. Steward A, Allott PR, Cowles AL, Mapleson WW. Solubility
greater protection of the myocardium than propofol in patients
coefficients for inhaled anaesthetics for water, oil and biological
undergoing off-pump coronary artery bypass surgery. Anesthe-
media. Br. J. Anaesth. 1973; 45: 282–93.
29. Weber NC, Toma O, Wolter JI et al. The noble gas xenon indu-
49. De Hert SG, ten Broecke PW, Mertens E et al. Sevoflurane but
ces pharmacological preconditioning in the rat heart in vivo via
not propofol preserves myocardial function in coronary surgery
induction of PKC-epsilon and p38 MAPK. Br. J. Pharmacol.
patients. Anesthesiology 2002; 97: 42–9.
50. Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC.
30. Rajakumaraswamy N, Ma D, Hossain M. Neuroprotective inter-
Volatile anesthetics mimic cardiac preconditioning by priming
action produced by xenon and dexmedetomidine on in vitro
the activation of mitochondrial K (ATP) channels via multiple
and in vivo neuronal injury models. Neurosci. Lett. 2006; 409:
signaling pathways. Anesthesiology 2002; 97: 4–14.
51. Kalenka A, Maurer MH, Feldmann RE, Kuschinsky W,
31. Geisslinger G, Hering W, Thomann P, Knoll R, Kamp HD,
Waschke KF. Volatile anesthetics evoke prolonged changes in
Brune K. Pharmacokinetics and pharmacodynamics of ket-
the proteome of the left ventricle myocardium: defining a mol-
amine enantiomers in surgical patients using a stereoselective
ecular basis of cardioprotection? Acta Anaesthesiol. Scand.
analytical method. Br. J. Anaesth. 1993; 70: 666–71.
Ó 2008 The AuthorsJournal compilation Ó 2008 Royal Australasian College of Surgeons
52. Cromheecke S, Pepermans V, Hendrickx E et al. Cardioprotec-
71. Struys MM, Kalmar AF, De Baerdemaeker LE et al. Time
tive properties of sevoflurane in patients undergoing aortic valve
course of inhaled anaesthetic drug delivery using a new multi-
replacement with cardiopulmonary bypass. Anesth. Analg.
functional closed-circuit anaesthesia ventilator. In vitro compar-
ison with a classical anaesthesia machine. Br. J. Anaesth. 2005;
53. Meiler SE. Long-term outcome after anesthesia and surgery:
remarks on the biology of a newly emerging principle in peri-
72. Eleveld DJ, Proost JH, Wierda JM. Evaluation of a closed-loop
operative care. Anesthesiol. Clin. 2006; 24: 255–78.
muscle relaxation control system. Anesth. Analg. 2005; 101:
54. Homburger JA, Meiler SE. Anesthesia drugs, immunity, and
long-term outcome. Curr. Opin. Anaesthesiol. 2006; 19: 423–8.
73. Nunes CS, Mahfouf M, Linkens DA, Peacock JE. Modelling
55. Budd K. Pain management: is opioid immunosuppression a clin-
and multivariable control in anaesthesia using neural-fuzzy
ical problem? Biomed. Pharmacother. 2006; 60: 310–17.
paradigms Part I. Classification of depth of anaesthesia and
56. Fanti L, Agostoni M, Arcidiacono PG et al. Target-controlled
development of a patient model. Artif. Intell. Med. 2005; 35:
infusion during monitored anesthesia care in patients undergo-
ing EUS: Propofol alone versus midazolam plus propofol. A
74. Cook TM, Hommers C. New airways for resuscitation? Resus-
prospective double-blind randomised controlled trial. Dig. Liver
75. Lai HY, Chen IH, Chen A. The use of the Glidescope for tra-
57. Wang LP, McLoughlin P, Paech MJ et al. Low and moderate
cheal intubation in patients with ankylosing spondylitis. Br. J.
remifentanil infusion rates do not alter target-controlled infu-
sion propofol concentrations necessary to maintain anesthesia
76. Bottcher-Haberzeth S, Dullenkopf A, Gitzelmann CA, Weiss M.
as assessed by bispectral index monitoring. Anesth. Analg.
Tracheal tube tip displacement during laparoscopy in children.
58. Thompson JP, Mahajan RP. Monitoring the monitors–beyond
77. Kneeshaw JD. Transoesophageal echocardiography (TOE) in
risk management. Br. J. Anaesth. 2006; 97: 1–3.
the operating room. Br. J. Anaesth. 2006; 97: 77–84.
59. Casati A, Fanelli G, Pietropaoli P et al. Continuous monitoring
78. Apfel CC, Kranke P, Katz MH et al. Volatile anaesthetics may
of cerebral oxygen saturation in elderly patients undergoing
be the main cause of early but not delayed postoperative vomit-
major abdominal surgery minimizes brain exposure to potential
ing: a randomized controlled trial of factorial design. Br. J.
hypoxia. Anesth. Analg. 2005; 101: 740–47.
60. Cafiero T, Di Iorio C, Di Minno RM. Non-invasive cardiac
79. Apfel CC, Stoecklein K, Lipfert P. PONV: a problem of inha-
monitoring by aortic blood flow determination in patients
lational anaesthesia? Best Pract. Res. Clin. Anaesthesiol. 2005;
undergoing hyperthermic intraperitoneal intraoperative chemo-
therapy. Minerva Anestesiol. 2006; 72: 207–15.
80. Milligan ED, Langer SJ, Sloane EM et al. Controlling patho-
61. Suttner S, Schollhorn T, Boldt J et al. Noninvasive assessment
logical pain by adenovirally driven spinal production of the anti-
of cardiac output using thoracic electrical bioimpedance in
inflammatory cytokine, interleukin-10. Eur. J. Neurosci. 2005;
hemodynamically stable and unstable patients after cardiac sur-
gery: a comparison with pulmonary artery thermodilution.
81. Lemmens LC, van Klei WA, Klazinga NS. The effect of
Intensive Care Med. 2006; 32: 2053–8.
national guidelines on the implementation of outpatient preop-
62. van Twest RM. Bispectral index guided timing of intubation
erative evaluation clinics in Dutch hospitals. Eur. J. Anaesthe-
without neuromuscular blockade during sevoflurane induction of
anaesthesia in adults. Anaesth. Intensive Care 2006; 34: 606–12.
82. Lanier WL. A three-decade perspective on anesthesia safety.
63. Vereecke HE, Vanluchene AL, Mortier EP et al. The effects of
ketamine and rocuronium on the A-Line auditory evoked poten-
83. Scott M. IOM ‘To err is human’. Available from URL: http://
tial index, Bispectral Index, and spectral entropy monitor during
steady state propofol and remifentanil anesthesia. Anesthesiol-
84. Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Post operative pain
experience: results from a national survey suggest postoperative
64. Vakkuri A, Yli-Hankala A, Sandin R et al. Spectral entropy
pain continues to be undermanaged. Anesth. Analg. 2003; 97:
monitoring is associated with reduced propofol use and faster
emergence in propofol-nitrous oxide-alfentanil anesthesia.
85. Scavone BM, Sproviero MT, McCarthy RJ et al. Development
of an objective scoring system for measurement of resident
65. White PF. Use of cerebral monitoring during anaesthesia: effect
performance on the human patient simulator. Anesthesiology
on recovery profile. Best Pract. Res. Clin. Anaesthesiol. 2006;
86. Practice guidelines for acute pain management in the perioper-
66. Hadzidiakos D, Petersen S, Baars J et al. Comparison of a new
ative setting. A report by the American Society of Anesthesiol-
composite index based on midlatency auditory evoked poten-
ogists Task Force on pain management, acute pain section.
tials and electroencephalographic parameters with bispectral
index (BIS) during moderate propofol sedation. Eur. J. Anaes-
87. McDonnell A, Nicholl J, Read SM. Acute pain teams and the
management of postoperative pain: a systematic review and
67. Takamatsu I, Ozaki M, Kazama T. Entropy indices vs the bis-
meta-analysis. J. Adv. Nurs. 2003; 41: 261–73.
pectral index for estimating nociception during sevoflurane
88. Werner MU, Soholm L, Rotboll-Nielsen P, Kehlet H. Does an
anaesthesia. Br. J. Anaesth. 2006; 96: 620–26.
acute pain service improve postoperative outcome? Anesth.
68. Ellerkmann RK, Soehle M, Alves TM et al. Spectral entropy
and bispectral index as measures of the electroencephalographic
89. Chaney MA. Intrathecal and epidural anesthesia and analgesia
effects of propofol. Anesth. Analg. 2006; 102: 1456–62.
for cardiac surgery. Anesth. Analg. 2006; 102: 45–64.
69. Struys MM, De Smet T, Greenwald S et al. Performance eva-
90. Gregoire N, Hovsepian L, Gualano V et al. Safety and pharma-
luation of two published closed-loop control systems using bis-
cokinetics of paracetamol following intravenous administration
pectral index monitoring: a simulation study. Anesthesiology
of 5 g during the first 24 h with a 2-g starting dose. Clin.
70. Baum JA. New and alternative delivery concepts and techni-
91. Keeble JE, Moore PK. Pharmacology and potential thera-
ques. Best Pract. Res. Clin. Anaesthesiol. 2005; 19: 415–28.
peutic applications of nitric oxide-releasing non-steroidal
Journal compilation Ó 2008 Royal Australasian College of Surgeons
anti-inflammatory and related nitric oxide-donating drugs. Br. J.
104. Tarride JE, Gordon A, Vera-Llonch M et al. Cost-effectiveness
of pregabalin for the management of neuropathic pain associ-
92. Dahl JB, Mathiesen O, Moiniche S. ‘Protective premedication’
ated with diabetic peripheral neuropathy and postherpetic neu-
an option with gabapentin and related drugs? Acta Anaesthesiol.
ralgia: a Canadian perspective. Clin. Ther. 2006; 28: 1922–34.
105. Stanton-Hicks M, Kapural L. An effective treatment of severe
93. Sharek PJ, Powers R, Koehn A, Anand KJ. Evaluation and
complex regional pain syndrome type 1 in a child using high
development of potentially better practices to improve pain
doses of intrathecal ziconotide. J. Pain Symptom Manage. 2006;
management of neonates. Pediatrics 2006; 118: S78–86.
94. Anand KJ. Clinical importance of pain and stress in preterm
106. Mitrirattanakul S, Ramakul N, Guerrero AV et al. Site-specific
neonates. Biol. Neonate 1998; 73: 1–9.
increases in peripheral cannabinoid receptors and their endog-
95. Anand KJ, Scalzo FM. Can adverse neonatal experiences alter
enous ligands in a model of neuropathic pain. Pain 2006; 126:
brain development and subsequent behavior? Biol. Neonate
107. Modell JH. Assessing the past and shaping the future of anes-
96. Shipton E, Shipton E. The pain epidemic: some proposed solu-
thesiology. Anesthesiology 2005; 102: 1050–57.
tions. N. Z. Med. J. 2005; 118: U1627.
108. Wang SY, Mitchell J, Wang GK. Preferential block of inactiva-
97. Eriksen J, Jensen MK, Sjogren P, Ekholm O, Rasmussen NK.
tion-deficient Na+ currents by capsaicin reveals a non-TRPV1
Epidemiology of chronic non-malignant pain in Denmark. Pain
receptor within the Na+ channel. Pain 2007; 127: 73–83.
109. Cheng JK, Chen CC, Yang JR, Chiou LC. The antiallodynic
98. Shipton EA, Tait B. Flagging the pain: preventing the burden of
action target of intrathecal gabapentin: Ca2+ channels, KATP
chronic pain by identifying and treating risk factors in acute
channels or N-methyl-d-aspartic acid receptors? Anesth. Analg.
pain. Eur. J. Anaesthesiol. 2005; 22: 405–12.
99. Evans C. Potential biologic therapies for the intervertebral disc.
110. Michel AD, Xing M, Thompson KM, et al. Decavanadate, a
J. Bone Joint Surg. Am. 2006; 88: S95–8.
P2X receptor antagonist, and its use to study ligand interactions
100. Taylor RS. Spinal cord stimulation in complex regional pain
with P2X7 receptors. Eur. J. Pharmacol. 2006; 534: 19–29.
syndrome and refractory neuropathic back and leg pain/failed
111. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain:
back surgery syndrome: results of a systematic review and
risk factors and prevention. Lancet 2006; 367: 1618–25.
meta-analysis. J. Pain Symptom Manage. 2006; 31: S13–19.
112. Kanai Y, Nakazato E, Fujiuchi A et al. Involvement of an
101. Zhou Y , Abdi S. Diagnosis and minimally invasive treatment of
increased spinal TRPV1 sensitization through its up-regulation
lumbar discogenic pain–a review of the literature. Clin. J. Pain
in mechanical allodynia of CCI rats. Neuropharmacology 2005;
102. Pflugmacher R, Beth P, Schroeder RJ et al. Balloon kyphoplasty
113. Sagar DR, Kelly S, Millns PJ et al. Inhibitory effects of CB1 and
for the treatment of pathological fractures in the thoracic and
CB2 receptor agonists on responses of DRG neurons and dorsal
lumbar spine caused by metastasis: one-year follow-up. Acta
horn neurons in neuropathic rats. Eur. J. Neurosci. 2005; 22:
103. Holt DV, Viscusi ER, Wordell CJ. Extended-duration agents
114. Parker BM. Anesthetics and anesthesia techniques: impacts on
for perioperative pain management. Curr. Pain Headache
perioperative management and postoperative outcomes. Cleve.
Ó 2008 The AuthorsJournal compilation Ó 2008 Royal Australasian College of Surgeons
Understanding and Managing Bisphosphonate Drugs and Oral Health ◊ Bisphosphonate drugs is a class of drugs use to treat certain disease states. The drug is administered orally or intravenously. The IV route medications (Zometa and Aredia) are used to treat primarily metastatic cancer and multiple myeloma. The oral medications are (Fosamax, Actonel, and Boniva) used primarily in the trea
Faculty of Resource Science and Technology, UNIMAS This course is a continuation from the basic course, STB1083Biochemistry. This course is designed to cover topics in thebiochemical reactions within and between the cells that will bedescribe in details in this course. Products generated from thebiosynthesis of either amino acids, protein, carbohydrate, fattyacid or lipids are broken down f