Vesna NOVAK-JANKOVIČ

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Regional anaesthesia in the ICUINTRODUCTIONIntensivists have become more and more interested in the preventionand the treatment of physiological and psychological stress in criticalill patients. Major surgery and major traumatic injury elicit profoundphysiological changes including hormonal, metabolic and immuno-logical responses. Many patients with a critical illness are in pain. Thealleviation of perioperative pain is primarily provided for humanitarianreasons but also to reduce nociception-induced responses, which mayadversely influence organ functioning and contributed to morbidity.Although there are only a few studies that scientifically document thisproblem, the facts are clear that pain is a major problem for patientshospitalised in intensive care units (1).A database search offers only a few articles regarding regional anaes-thesia and critical ill patients. A pain is widely recognised as theso-called »fifth vital sign« and its assessment in the intensive care unit(ICU) can be difficult. Many patients in the ICU are not able to com-municate so alternative assessment tools such as physiological responsesto painful stimuli, changes of heart rate and blood pressure, grimacing,sedation Ramsay score and so on might be helpful (2).Regional anaesthesia and analgesia may result in improvementscritically ill patient outcomes.REGIONAL ANAESTHETIC TECHNIQUESAnimal data have shown that blockade of noxious stimuli from theperiphery can reduce the phenomenon of spinal cord excitation, andthus reduce pain and analgesia requirements. After tissue injury or in-flammation acute pain messages start with the excitation of primary af-ferent nociceptors and the excitation of the myelinated (A-d) or un-myelinated neurons (C-fiber) occurred. Afferent input from large andsmall-fiber activation is balanced in the dorsal horn. Descending path-ways (excitatory and inhibitory) modulate pain transduction by pri-mary afferents. Alteration in the balance of these factors can result ininhibition (analgesia) or stimulation (hyperalgesia)(3). Regional an-aesthesia and analgesia refers to techniques that use needles, catheters,and infusion devices to deliver drugs in close proximity to peripheralnerves, plexuses, nerve roots, ganglia, or directly into spinal fluid. Re-gional analgesia often is defined by the impulse-blocking action of localanaesthetic agents. Local anaesthetic agents interfere with voltage--gated sodium channels impeding or eliminating axonal impulse prop-agation. Drugs may be applied directly to the site of injury or directed tothe nerves that subserve the general area of injury. Targets includenociceptors, mixed nerves, plexuses, ganglia and segments of the spinalcord. Local anaesthetic agents remain the first-line agents used in re-VESNA NOVAK-JANKOVI^Clinical Department of Anaesthesiologyand Intensive therapyUniversity Medical Centre Ljubljana, SloveniaE-mail: vnjankovic@hotmail.comReceived March 11, 2009.PERIODICUM BIOLOGORUM UDC 57:61VOL. 111, No 2, 285–288, 2009 CODEN PDBIADISSN 0031-5362Clinical experiencegional analgesia. Adrenaline is often added to local an-aesthetic agents to reduce intravenous uptake and to pro-long the effects of the block. The alpha 2 agonists haveantinociceptive properties and have been used as ad-juncts to local anaesthetic agents at various anatomic lev-els. Clonidine potentiates opioid analgesia when appliedneuraxially (Table 1).Epidural analgesiaEpidural analgesia is probably the regional anaes-thetic technique most often used in the ICU. Epiduralanaesthesia is defined as the intraoperative use of localanaesthetics and opioids and epidural analgesia is de-fined as the postoperative use of local anaesthetics oropioids (4). Indications for epidural analgesia in the ICUinclude chest trauma, thoracic and abdominal surgery,major vascular surgery, major orthopaedic surgery, acutepancreatitis, paralytic ileus, cardiac surgery and intracta-ble angina pain. Contraindications for the placement ofepidural catheters are: current sepsis, bacteremia andcoagulopathies (Table 2).Cardiac morbidity is the most common cause of deathafter major surgical procedures. Thoracic epidural an-aesthesia (TEA) with local anaesthetics can produce aselective segmental blockade of the cardiac sympatheticinnervations (T1-T5). Excessive activation of the cardiacsympathetic nervous system by surgical stress has beendemonstrated to increase myocardial oxygen demand,while inducing coronary artery vasoconstriction (de-creasing supply), thus resulting in clinical correlates ofmyocardial ischemia such as ST segment changes, an-gina and disrrhythmias. TEA blunts these adverse effectsof surgical stress with increase of blood flow to ischemicregions of myocardium, so TEA thus improves the bal-ance between cardiac supply and demand.Epidural and to a lesser extent, intraspinal opioid de-livery has become a common method for pain control insurgical intensive care. Evidence indicates that the dorsalhorn is the site of action for regional opioid activity.Studies indicate that the onset of analgesic action fromepidural or subarachnoid opioids is proportional to thelipid solubility of the opioid administered. Hydrophilicopioids are transported in the cerebrospinal fluid stream.Opioid analgesicsAll opioids in clinical use produce analgesia with thesame molecular mechanism, binding to G-protein cou-pled opioid receptors with subsequent inhibition ofadenylate cyclase, activation of inwardly rectifying potas-sium channels, and inhibition of voltage-gated sodiumchannels, all of which decrease neuronal excitability. Alarge part of the explanation for pharmacologic differ-ences among opioids lies in the fact that opioids differ intheir ability to reach opioid receptors. Epiduraly admin-istered opioids must traverse the dura and arachnoid ma-ter, diffuse through cerebrospinal fluid, traverse the piamater to reach the surface of the spinal cord, diffusethrough the white mater and than the gray mater soreach opioid in the dorsal horn.Studies demonstrate that the only mechanism by whichdrugs redistribute from the epidural space to the spinalcord is diffusion through the spinal meninges. The pre-cise mechanism involved in epidurally administered li-pid-soluble opioids is a matter of controversy. The blockingof pain by lipid-soluble opioids after epidural adminis-tration is more the result of systemic uptake than a directeffects on spinal opioid receptors. Continuous fentanylinfusion as the sole agent for epidural analgesia appearsto produce analgesia by systemic uptake and redistribu-tion to brain. Continuous fentanyl infusion produced thesame quality analgesia, the same side effects, requiredthe same fentanyl dose and produced the same fentanyl286 Period biol, Vol 111, No 2, 2009.Vesna Novak-Jankovi~ Regional anaesthesia in the ICUTABLE 1Drugs used for regional anaesthesia and analgesia.Anaesthetics and analgesics Site of action Anatomic locationLocal anaesthetics Sodium channel blockers All locationsOpioid analgesics G-protein opioid receptors Peripheral, epidural, subarachnoidalClonidine Alpha-2 adrenergic receptors Subarachnoidal, epidural, peripheralNeostigmin Increases acetylcholine Subarachnoidal, epiduralMidazolam GABA receptors EpiduralKetamine NMDA receptor antagonist EpiduralTABLE 2Indications and contraindications for epidural analgesiain ICU.Indications ContraindicationsChest traumaThoracic surgeryAbdominal surgeryParalytic ileusPancreatitisIntractable anginaVascular surgeryOrthopaedic surgeryTrauma of lowerextremitiesPatient refusalCoagulopathyThrombolytic therapyIncreased ICPSepsisLocal infection at puncture siteSevere hypovolemiaAcute haemodynamic instabilityObstructive ileusplasma concentration whether the drug was infused in-travenously or epidurally. Approximately 10% more su-fentanyl infusion is needed for postoperative analgesia bythe epidural than by the intravenous route. Morphineclearly produces analgesia by spinal mechanism whetheradministered epidurally or intrathecally and it shouldprobably be considered the »gold standard« for spinallyadministered opioids. Morphine is hydrophilic and spreadsquickly in the cerebrospinal fluid and it is therefore ableto produce analgesia in thoracic region even when it isinjected into the caudal epidural space. Only ¼ as muchmorphine is required epidurally as intravenously forpostoperative pain relief. Morphine remains the drug ofchoice for epidural administration because its decreaseddose, improves pain relief and may diminish seriousmorbidity and mortality in high risk surgical patientscompares with standard parenteral administration. How-ever, spinal pharmacokinetics of these drugs are complexand, in some ways, counterintuitive.Clonidine is a selective alpha-2 adrenergic agonistwith some alpha-1 agonist property (200:1). Clonidineproduces analgesia through stimulation of alpha-2 adreno-ceptors located in the dorsal horn of the spinal cord. Thecombined epidural administration of clonidine (1–4 mgkg-1) with a local anaesthetic improves the block andprolongs postoperative analgesia.Ketamine has recently been utilised in spinal anaes-thesia. Ketamine provides deep analgesia by acting as an-tagonist at the level of NMDA receptors present through-out the central nervous system. Epidural ketamine giveslonger lasting analgesia than intramuscular ketaminewhile the blood levels are similar.Local anaesthetic agentsBupivacaine, racemic mixture of two enantiomers isthe most commonly used local anaesthetic agents forepidural anaesthesia and analgesia. The dose of local an-aesthetic in the thoracic region and in the pregnant,obese and elderly patients is reduced about 15–30%.Ropivacaine is chemically related to mepivacaine andbupivacaine, but differs in its molecular structure andbeing the first marketed enantiomeric local anaesthetic.Ropivacaine is less cardiotoxic than equimolar con-centrations of bupivacaine and epidural ropivacaine isless potent than epidural bupivacaine when the twodrugs are administered at the same concentration. Nev-ertheless, higher doses of ropivacaine than bupivacaineare generally required to elicit equivalent anaesthetic ef-fects. Ropivacaine is reported to demonstrate a greaterdegree of separation between motor and sensory block-ade compared to bupivacaine. Ropivacaine provides ef-fective analgesia with minimal motor block and earlymobilisation during labour and after surgery.Levobupivacaine is the pure S-enantiomer of bupi-vacaine. In preclinical in vitro and in vivo animal studies,levobupivacaine has demonstrated the potency similar tobupivacaine which exerting significantly less central ner-vous system and cardiovascular system toxicity (5).Subarachnoid analgesiaAlthough subarachnoid anaesthesia is commonly usedfor many surgical procedures, analgesia from a single in-jection of local anaesthetics does not last long enough to beuseful for postoperative pain relief. The use of continuoussubarachnoid analgesia has been reported. Subarachnoidcatheters are effective means for delivering medications tothe spinal fluid for distribution to the spinal cord. Preser-vative free nontoxic preparations must be used to avoid thepotential for pathologic alteration of the spinal cord. Spi-nal administration ensures transport of medications to thespinal fluid and reduces the mass of the medicationneeded. Catheters can be used safely for days to months.The risk for infection is substantial, however (6).Paravertebral blocksParavertebral blocks (PVB) produce unilateral trunkanaesthesia by blocking the segmental nerves of the spinalcord. Thoracic PVB was first performed in 1906 bySelheim and is thus amongst the oldest of local anaesthetictechniques. In 1912 Kappis used lumbar PVB for urologi-cal surgery. Eason and Wyatt stimulated renewed interestfor PVB when they described the insertion of a catheterinto the thoracic paravertebral space (PVS). The new en-thusiasm for PVB has occurred to decrease cardiovascularand respiratory effects of central neuraxial blocks, and todecrease side effects associated with general anaesthesiaand narcotics. The PVS is bounded by the vertebral bodymedially, the transverse process and costotransverse liga-ment superficially and parietal pleura laterally. The lum-bar PVS is not continuous with thoracic PVS. The PVScontains the dorsal and ventral rami of the spinal roots aswell as sympathetic fibers of the ventral rami. Thus localanaesthetic introduced into the PVS can provide a unilat-eral motor, sensory and sympathetic block.PVB can provide anaesthesia and excellent postopera-tive analgesia for breast surgery, thoracic surgery (lung,rib resections), abdominal surgery, minimal invasive car-diac surgery, rib fractures, and can be used for treatmentof chronic pain.Inadvertent intravascular injection of excessive dosesof local anaesthetics can result in toxicity. Because of theclose ralationship of the paravertebral space to the parietalpleura, inadvertent needle placement can cause pneumo-thorax.Incorrect medial needle insertion can result in epi-dural or spinal blockade.Intrapleural analgesiaIntrapleural analgesia may be used for postthoraco-tomy pain. Its use has also been described following lap-aroscopic cystectomy, cholecystectomy, herpes zoster andnephrectomy. Intrapleural catheters relly on local anaes-thetic spread throughout to intrapleural space and there-fore require significant volumes of local anaesthetic. Pa-tinets with chest tubes often drain a significant portion ofmedication before the medication is delivered to the ac-tive site.Period biol, Vol 111, No 2, 2009. 287Regional anaesthesia in the ICU Vesna Novak-Jankovi~Brachial plexus blockadeThere are number of approaches to blocking thebrachial plexus to provide anaesthesia or analgesia to theupper extremity. The interscalene block involves injectinglocal anaesthetic immediately lateral to the exiting C6nerve route. This block provides excellent pain relief to theshoulder and upper arm. Supraclavicular approach forbrachial plexus blockade can provide excellent analgesiathroughout to entire upper extremity including the shoul-der. There is a significant risk for pneumothorax andfrenic nerve block is also common with this technique.Axillary block is considered one of the safest approaches tothe brachial plexus but axillary approaches do not provideanalgesia to the shoulder consistently.Femoral block and schiatic nerve blocksFemoral nerve blocks with catheter technique canprovide adequate analgesia for the anterior thigh or moredistal pain in the saphenous nerve distribution withoutthe haemodynamic changes associated with neuraxialblocks. Sciatic nerve blocks can provide good analgesia tothe posterior thigh and the distal lower extremity not inthe saphenous distribution.SURGICAL OUTCOMEMultiple comparisons of neuraxial blockade to generalanaesthesia and a recent meta-analysis of these compari-sons shows a significant reduction in mortality and mor-bidity with regional techniques. The first study on thistopic suggesting that postoperative epidural opioid usemay decrease patient mortality by Yeager et al. appeared in1987 (7). The results of this study showed that intra-operative epidural anaesthesia with local anaesthetics fol-lowed by postoperative epidural narcotic analgesia in highrisk patients significantly decreased patient mortality, car-diac failure, infections, hospital and physician costs. Raggiet al. have shown that a combination of the epidural tech-nique using local anaesthetics intraoperatively and mor-phine postoperatively offers many advantages. These ben-efits include inhibition of the surgical stress response,decreased cardiorespiratory depression, blood loss, intuba-tion time and pulmonary infection, thromboembolism,hyperglycemia, hypertensive response, nitrogen sparing,prevention of immunosupression, and enabled earlier am-bulation and hospital discharge (8).Although epidural anaesthesia and analgesia may im-prove the outcome in high-risk patient population, po-tential benefits in low-risk population remain poorly de-fined because of the low rate of morbidity in these patientgroups. Significant beneficial effects of epidural analge-sia have been observed only for intermediate outcomesnot for ultimate patient outcome. Future studies requireformation of multicenter study groups and necessitateenrolment of thousands of patients.However regional anaesthesia is not a panacea, but inthe right patients and the right situations it can improvesurgical outcome (9).A more complex , multimodal approach to periopera-tive treatmant is widely accepted and recommended bymany. After colonic operations, combined approach ofoptimal pain relief with balanced analgesia,enforced earlymobilisation,and oral feeding, may reduce the length ofcovalescence and hospital stay after colonic operations(10). Recovery after abdominothoracic oesophageal re-section may be improved by the introduction of intraope-rative TEA, postoperative PCEA, earlier extubation,andearly mobilisation of the patient (11).CONCLUSIONSNociception is a complicated process and only in re-cent years have the neural pathways and mediator ofpain transmissions been unravelled. Used wisely, the re-gional techniques, can provide excellent pain controland may have significant role in improving overall pa-tient outcome. Well-conducted regional analgesia offersthe best opportunity to provide substantional analgesiawithout significant central opioid effects. Regional anal-gesia using single injection regional blocks and continu-ous neuraxial and peripheral catheters can play a valu-able role in a multimodal approach to pain managementin the criticaly ill patients to reduce physiologic and psy-chological stress.REFERENCES1. SCHULZ-STÜBNER S, BOEZAART A, HATA S 2005 Regionalanalgesia in the critically ill. Crit Care Med 33: 1400–72. SCHULZ-STÜBNER S 2006 The critically ill patient and regionalanesthesia. Current Opinion in Anaesthesiology 9: 538–443. ClaRK F, GILBERT H C 2001Regional analgesia in the intensivecare unit. Principle and practice. In: Vender J S V, Szokol J W, MurhyG S (eds) Critical Care Clinics. Sedation, analgesia and neuromus-cular blockers in critical care medicine. W.B. Saunders Company,Philadelphia, London, Toronto etc., p 9434. LIU S, CARPENTER R L, NEAL J M 1995 Epidural anesthesiaand analgesia. Their role in postoperative outcome. Anesthesiology82: 1474–5065. NOVAK-JANKOVI^ V 2005 Analgesia in major abdomiothoracicsurgery. Lije~ Vjesn 127(Suppl.2): 6–106. STEVENS D S, EDWARDS W T 2002 Management of pain in thecritically ill. In: Irwin R S, Rippe J M (eds) Irwin and Rippe’s Inten-sive care medicine. Fifth edition. Lippincott Williams & Wilkins,Philadelphia, Baltimore, New York etc., p 17327. YEAGER M P, GLASS D D, NEFF R K et al. 1987 Epidural anes-thesia and analgesia in high risk surgical patients. Anesthesiology 66:729–368. RAGGGI R, DARDIK H, MAURO A L 1987 Continuous epiduralanaesthesia and postoperative epidural narcotics in vascular surgery.Amer J Surg 154: 192–79. BALLANTYNE J 2001 Does regional anaesthesia improve out-come after surgery. Refresher course lectures. Gothenburg. 9th ESAAnnual Meeting, p 4110. MOINICHE S, BULOW S, HESSELFELDT P et al. 1995 Conva-lescence and hospital stay after colonic surgery with balanced anal-gesia, early oral feeding, and enforced mobilisation. Eur J Surg 161:283–811. BRODNER G, POGATZKI E, VAN AKEN H et al. 1998 A multi-modal approach to control postoperative pathophysiology and reha-bilitation in patients undergoing abdominothoracic esophagectomy.Anesth Analg 86: 228–34288 Period biol, Vol 111, No 2, 2009.Vesna Novak-Jankovi~ Regional anaesthesia in the ICU

Regional anaesthesia in the ICU

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