ARTICLE IN PRESS

Current Anaesthesia & Critical Care (2006) 17, 85–91

0953-7112/$ - sdoi:10.1016/j.c

�Tel.: +44 16E-mail addr

www.elsevier.com/locate/cacc

FOCUS ON: CONSIDERATIONS DURING THE POSTOPERATIVE PERIOD

Pruritus and anaesthesia

Tim Meek�

James Cook University Hospital, Middlesbrough TS4 3BW, UK

KEYWORDSPruritus;Anaesthesia;Anaesthesiology;Analgesics—opioids

ee front matter & 2006acc.2006.05.004

42 854600; fax: +44 146ess: tim.meek@stees.n

Summary Pruritus is a common complication of anaesthesia. In this article,current knowledge regarding the pathophysiology and treatment of the condition arepresented. A suggested approach for treatment is given.& 2006 Elsevier Ltd. All rights reserved.

Itching is common in the postoperative period.Often it is no more than a minor nuisance, or atransient phase but it may be a severely trouble-some problem for some patients. Despite this, eventhe largest of anaesthesia textbooks often devoteonly a paragraph or two to the topic. The aim ofthis article is to summarize current knowledgeregarding the condition, and to suggest a practicalapproach to treating it.

Definition

Itch is defined simply as a sensation, arising fromthe skin or a mucous membrane, which producesthe desire to scratch. Itch is benign, occurringspontaneously, or secondary to irritation from anexternal stimulus, such as a woolly jumper. If itch ispathological, it is termed pruritus. For that reason,the term pruritus is used in this article. Measure-ment scores using visual analogues scales andfrequency of itching are commonly described.These are useful in scientific studies of the

Elsevier Ltd. All rights reserv

2 282818.hs.uk.

phenomenon, but are of less use in the day-to-daytreatment of sufferers.

Transmission pathways of itch

The precise mechanism of itch transmission isincompletely understood. However, current knowl-edge has been comprehensively summarized.1 Itchwas previously taken to be simply a sub-modality ofpain. This is now known not to be the case. Itstransmission involves a sub-population of thenocioceptive C-fibres, which unlike their painanalogues, are insensitive to mechanical stimula-tion, but sensitive to histamine. These primaryneurones travel to the ipsilateral dorsal horn of thespinal column and synapse there with a specificsecondary itch neurone. These cross immediatelyto the contralateral anterolateral spinothalamictract, and radiate to the thalamus. There, theysynapse with a tertiary neurone, which projects tothe somatosensory cortex, specifically the post-central gyrus (Fig. 1). There is evidence ofactivation of the supplementary motor area,perhaps in preparation for the action of scratching.Although distinct from pain transmission, there is

ed.

ARTICLE IN PRESS

Figure 1 Diagrammatic representation of transmissionpathway of itch. Primary, secondary and tertiary afferentneurones marked 1, 2 and 3, respectively.

T. Meek86

some evidence of interaction between the twomodalities, with each able to inhibit transmission ofthe other.

Substances mediating pruritus

A number of substances act or are postulated to actas mediators in the transmission or potentiation ofpruritus. Knowledge of these aids understandingand planning of anti-pruritus treatments.

Histamine

This is the most commonly known potentiator ofitch, and the one which is most commonly targetedin simple anti-pruritus treatment. Histamine isreleased in the epidermis from mast cells inresponse to a number of stimuli, and stimulatesH1 receptors in the epidermal C-itch fibres. Eighty-five percent of epidermal receptors are H1 recep-tors; the rest are H2.

2 Histamine is only implicatedin itch due to mast cell degranulation, such asallergic, insect bite or following drug-relatedhistamine release.

Arachidonic acid derivatives

Prostaglandins may fulfil the same role in poten-tiating and sensitizing itch receptors, as they dowith pain receptors. Leukotrienes also appearto have a potentiating effect. Non-steroidal

anti-inflammatory drugs (NSAIDs) have been shownto reduce pruritus in allergic conjunctivitis. Ninetypercent of those given ketorolac reported improve-ment in their symptoms.3 Following anaesthesia forabdominal surgery including epidural fentanyl, theeffect of tenoxicam was studied.4 The tenoxicamgroup had less pruritus, but also had lower painscores and used less pethidine. This may explainthe lower incidence of pruritus. However, when thecyclo-oxygenase 2 inhibitor celecoxib was given towomen receiving spinal anaesthesia using bupiva-caine and morphine, no effect on incidence ofpruritus was shown.5 These findings suggest thatthere may be a role for NSAIDs in the preventionand/or treatment of itch, but clearly there is muchmore to be researched yet.

Serotonin

The observation in some studies that 5-HT3 antago-nists can successfully treat resistant itch in a smallgroup of patients has led to the postulation that 5-HT3 receptor is involved in itch. Ondansetron is themost studied drug (see below).

Others

Intradermally, acetyl choline does not elicit itch innormal individuals (rather pain), but in atopicindividuals, itch is elicited. Peptides can mediateitch, either via or without histamine release (suchas bradykinin and Substance P, respectively).Protease enzymes liberated during tissue damagehave been implicated. Cytokines are involved insome forms of itch.

Anaesthesia-related causes of itch

Opioids

These probably represent the most common anaes-thetic-related cause of pruritus. Pruritus can occuras a result of systemic or neuraxial administration.It appears that systemic administration causespruritus via peripheral and central mechanisms,whereas neuraxial route acts solely via centralmechanisms.

Systemic mechanismsOpioids cause histamine release via non-immune-mediated degranulation of mast cells, which in turncauses itch. Administration of simple anti-hista-mine drugs can reverse this type of pruritus, butnot always. This implies that some of the pruritus is

ARTICLE IN PRESS

Pruritus and anaesthesia 87

mediated centrally, as opioid reaches the brain viathe circulation. When some opioids (e.g. morphinebut not fentanyl) are introduced intradermally, awheal and flare is seen. Pruritus in this context hasbeen shown to be reduced by the administration ofanti-histamines (H1), but not by naloxone, impli-cating histamine as the major culprit.6–8 If H2

blocking anti-histamines are used, they are noteffective alone, but can augment the effect of anH1 blocking anti-histamine.9 There is also immuno-histochemical evidence of ‘micro-opioid receptors’in cutaneous nerves which may be involved in thegenesis of pruritus, supporting some researchshowing that opioid antagonists can cause reduc-tion in this type of pruritus.10

Neuraxial mechanismsThe cause of pruritus in this context is multi-factorial, and there are many postulated mechan-isms. Much remains to be elucidated. In vitro,superficial dorsal horn neurones respond to prur-itogenic stimuli and thus might participate intransmitting itch. Low concentrations of morphineapplied to these neurones resulted in facilitation ofsuperficial neuronal responses to histamine,coupled with inhibition of deep dorsal hornneurones, which might underlie the developmentof pruritus that is often observed after epiduralmorphine.11 However, naloxone did not reverse theeffects in all cases. It has also been postulated thatmorphine inhibits some dorsal horn neurones,which then facilitates transmission of itch by otherpathways. After intrathecal and epidural adminis-tration of opioids, there is cephalad spread of drugin the cerebrospinal fluid, causing pruritus via acentral mechanism.12 However, there are m-recep-tors in the dorsal horn of the spinal cord, which maybe involved in itch. In animal studies, itch has beeninduced by intramedullary morphine injection, andis probably mediated via m-receptors.6,13,14 For thisreason m-receptor antagonists are effective againstthis type of pruritus, but their use runs the risk ofalso reversing analgesia. The use of partial antago-nists may be one way of mitigating this risk.

Other drugs

Hydroxyethylstarch (HES) is a high-molecular-weight colloid solution. Pruritus is an often quotedside-effect of this drug. In one study, skin biopsiesof patients with itch following HES administrationunderwent immunoelectron microscopic investiga-tion using an antibody highly specific for HES. Smallperipheral nerves showed vacuoles containing HESdeposits, and disappearance of these deposits over

time paralleled improvement in pruritic symptoms.HES deposits in cutaneous nerves may thereforeaccount for the itching seen after infusion.15

Pruritus of this cause has been successfully treatedwith topical capsaicin.

Antibiotics may cause pruritus via non-immune-related degranulation of mast cells, with subse-quent release of histamine. This may occur alongwith other histamine-related side-effects, withanaphylaxis being the most severe. Treatment ofuncomplicated cases begins with anti-histaminedrugs.

Other causes of pruritus

There are many pathological conditions that pre-dispose individuals to itch and pruritus. A compre-hensive review is beyond the scope of this paper,but the topic has recently been reviewed in detailelsewhere.1 Pruritus is common in chronic (but notacute) renal failure, where it may be due toaccumulation of pruritogenic chemicals. Improve-ments in the technology of dialysis have reducedthe incidence in such patients; transplantation iscurative. In the absence of this, many and variedtreatments have been described, including physicalmethods as well as partial opioid agonists andondansetron. Patients with hepatic disease com-monly report pruritus. It is common in jaundicesecondary to cholestasis, and the incidence is 100%in primary biliary cirrhosis. Again, many treatmentsare described, including drugs to reverse choles-tasis or to enhance elimination of bile acids.Haematological disorders can cause pruritus, suchas polycythaemia rubra vera (approximate inci-dence 50%), Hodgkin’s disease (30%) and T-celllymphoma (100%). Varied treatments are de-scribed, but the best is treatment of the underlyingcondition. Neurological causes of pruritus includeshingles, where post-herpetic itching is a phenom-enon in some patients, and central neurologicalpruritus, a rare condition where itching is asymptom of another neurological condition. Othercauses of pruritus include Helicobacter pyloriinfection, paraneoplastic syndrome and of coursesome dermatological conditions.

Obstetric

Obstetric cholestasis (OC) is a pregnancy-specificliver condition presenting typically with palmarand/or plantar pruritus without rash in the latesecond or third trimester.16 It has ethnic, familial

ARTICLE IN PRESS

T. Meek88

and genetic preponderances. For instance, theincidence is around 1% of pregnancies in Europe,but 10 times that number in South America. Thesurge in pregnancy steroid hormones may result ingenetically predisposed women developing choles-tasis. The condition is also associated with in-creased perinatal morbidity and mortality.Accurate diagnosis relies on a high index ofsuspicion, abnormal liver function tests and raisedserum bile acid levels after the exclusion of otherorganic causes of liver disease. Ursodeoxycholicacid, along with active management of pregnancy,is the treatment of choice. Following delivery,there is usually a dramatic improvement. There ishigh risk of recurrence in subsequent pregnancies.OC sufferers should be warned of the risk thatanaesthetic interventions will worsen their prur-itus. Even in routine obstetric anaesthesia, anaes-thesia-related pruritus is frequently encountered,as there is a high rate of use of neuraxialtechniques, most usually with opioid and becausepregnant women are more susceptible to itch thannon-pregnant patients.17 Treatment approach isgenerally as per the non-pregnant patient. Thedistraction of labour means that pruritus is morefrequently complained of post-delivery, so fetaltransfer of drugs is often not a worry. Excretion ofdrug into breast milk is a consideration, althoughmost of the routine drugs are commonly used in thissituation.

A practical approach to treatinganaesthesia-related pruritus

Drug choice

The best treatment is of course avoidance ofcausative agents. To the anaesthetist, this meansavoidance of HES solutions, unless clinically indi-cated. It also implies avoidance of opioids by anyroute if at all possible. However, anaesthetists’clinical practice most often demands the use ofopioids, and so selection of an appropriate dose isvital. For intravenous opioids, titration of theminimum possible dose to achieve analgesia issensible practice. In the context of intrathecaldiamorphine in caesarean section, 400mcg appearsto be the optimum dose (maximum balance ofanalgesic effect vs. side-effects), when combinedwith hyperbaric bupivacaine 0.5% 12.5mg.18

The use of peri-operative NSAIDs may be beneficial,if not via a direct pharmacological effect,then at least by reducing consumption of opioidanalgesics.

Non-pharmacological treatments

Skin cooling has been shown to be useful. This canbe achieved in many ways, but a cool pack isperhaps the simplest. The application of variousointments has been described, with calamine lotion(an emulsion of calamine, zinc oxide, glycerol,bentonite, sodium citrate and liquefied phenol)being the most well known. E45s or other similarhydrating cream may be useful. If itch is mild, anexplanation of the reasons for and the transientnature of the problem may be enough reassuranceto many patients, and may avoid the need for anypharmacological treatment.

Pharmacological treatments

Anti-histaminesThese are perhaps the best-known treatment forpruritus. In the UK, a suitable first line treatment isthe H1 histamine antagonist chlorphenamine, withdoses of 10mg repeated every 6 h if needed. It canbe given orally or intravenously, depending onclinical need. It is most appropriate if the pruritusis due to a systemic drug causing peripheralhistamine release (e.g. morphine). Addition of anH2 histamine receptor antagonist such as ranitidinecould be considered in resistant pruritus of thistype, before moving on to other treatments. Thisitch has been shown to be useful in chronic itchconditions.19,20 Anti-histamine drugs can be usefulin the treatment of pruritus due to neuraxialopioids. Although this might appear initially un-likely, it may be simply related to their sedatingaction. For this reason, and because of therelatively benign side-effect profile, chlorphena-mine is a reasonable first line drug even in thisgroup of patients.

Opioid antagonists

CompleteIntravenous naloxone provides excellent relief ofpruritus of neuraxial opioids. However, the reliefmay be transient, and may reverse the analgesiceffect of the opioids component. Perhaps moreimaginative ways of delivering it would provide amore useful profile. When given in one study as anultra-low dose co-delivered along with morphine bypatient controlled analgesia, incidence of prurituswas lower than with morphine alone,21 althoughanother study failed to demonstrate this benefit.22

It is also effective when given via epidural alongwith morphine,23 or via epidural as part of

ARTICLE IN PRESS

Pruritus and anaesthesia 89

combined spinal-epidural analgesia in labour usingbupivacaine with fentanyl.24

PartialIf reversal of analgesia is to be avoided, it ispossible to treat opioid-induced pruritus usingpartial opioid antagonists. Successful treatmentshave been described using intravenous nalbuphine,counteracting epidural fentanyl-induced pruritus.25

Substituting epidural morphine for butorphanol hasbeen shown to decrease significantly the incidenceof pruritus after caesarean delivery.26 Similarresults were found when comparing buprenorphinewith fentanyl, although buprenorphine was morecommonly associated with distressing vomiting.27

Buprenorphine is the only drug of this typeavailable in the UK. It has been described withsome success as a treatment for cancer-related,28

and hepatic disease-related, cholestatic pruritus,29

but there are no significant studies of its useas a treatment for the pruritus of opioids admin-istration.

Ondansetron

Studies have demonstrated efficacy against pruritusinduced by intrathecal morphine30–33 and epiduralmorphine.33,34 However, morphine is not commonlyused in the UK in this way; fentanyl and diamor-phine are more commonly used. Ondansetron hadno significant effect on pruritus induced by in-trathecal fentanyl as part of labour analgesia,35 norin knee arthroscopy.36 However, other work hasdisputed these findings.37,38 There appears to be nopublished work looking at the effect of ondansetronon pruritus secondary to intrathecal or epiduraldiamorphine

Propofol

Sub-hypnotic doses of propofol have been studiedas anti-pruritus treatment. When compared withnalbuphine, in patients who had received intrathe-cal morphine during anaesthesia for caesareansection, nalbuphine was superior.39 No benefit wasshown when it was compared with Intralipid inpatients who had received intrathecal morphine forarthroplasty,40 nor when compared with placebofor the same following caesarean section.41,42

However, other work in similar situations hassupported propofol’s use.43,44 When compared withnaloxone in treatment of epidural morphine-in-duced pruritus, it was equally effective, but therewas a higher incidence of pain following naloxoneuse.45 There appears to be no work looking at its

use against pruritus caused by neuraxial fentanyl ordiamorphine.

Alizapride

This is a new methoxybenzamide anti-emetic,currently unavailable in the UK. It works byinhibiting dopaminergic D2 receptor. It has beenshown in trials46 to reduce intensity but notincidence of itch in patients receiving spinalanaesthesia including morphine for caesarean sec-tion, compared with metoclopramide. However,metoclopramide (the closest equivalent drug avail-able in the UK) has been shown to be ineffective inthis regard.47

Summary

Pruritus is commonly seen in association withanaesthesia, and so anaesthetists need to have aplan of action. The best option is avoidance ofcausative agents where possible. Peri-operativeNSAIDs are recommended. When pruritus is aproblem, an H1 histamine antagonist is a good firstline treatment, particularly where the pruritus isdue to a systemic drug, with likely histaminerelease. Addition of an H2 blocker may confer asmall benefit. Where a neuraxial opioid is theculprit, histamine antagonists may still help, withthe reassurance of little adverse effect if they donot. However, a meta-analysis of the literature upto the year 2000 only found evidence of anti-pruritic efficacy for m-receptor antagonists anddroperidol (now unavailable).48 Judicious use ofintravenous naloxone will improve the situation,but care must be taken not to reverse analgesia.The usefulness of other routes of administration fornaloxone remains to be proven. Buprenorphine isan alternative to naloxone, although the lack ofdata in the majority of clinical situations leavesdosages and timings to the individual clinician. Theconflicting evidence surrounding propofol andondansetron in the treatment of pruritus makes itdifficult to recommend their use yet, other thanperhaps when conventional treatments have failed.

References

1. Waxler B, Dadabhoy ZP, Stojiljkovic L, Rabito SF. Primer ofpostoperative pruritus for anesthesiologists. Anesthesiology2005;103(1):168–78.

2. Kaplan AP. Clinical practice. Chronic urticaria and angioe-dema. N Engl J Med 2002;346(3):175–9.

ARTICLE IN PRESS

T. Meek90

3. Raizman MB. Results of a survey of patients with ocularallergy treated with topical ketorolac tromethamine. ClinTher 1995;17(5):882–90.

4. Colbert S, O’Hanlon DM, Chambers F, Moriarty DC. Theeffect of intravenous tenoxicam on pruritus in patientsreceiving epidural fentanyl. Anaesthesia 1999;54(1):76–80.

5. Lee LH, Irwin MG, Lim J, Wong CK. The effect of celecoxibon intrathecal morphine-induced pruritus in patients under-going Caesarean section. Anaesthesia 2004;59(9):876–80.

6. Szarvas S, Harmon D, Murphy D. Neuraxial opioid-inducedpruritus: a review. J Clin Anesth 2003;15(3):234–9.

7. Saucedo R, Erill S. Morphine-induced skin wheals: a possiblemodel for the study of histamine release. Clin PharmacolTher 1985;38(4):365–70.

8. Hermens JM, Ebertz JM, Hanifin JM, Hirshman CA. Compar-ison of histamine release in human skin mast cells inducedby morphine, fentanyl, and oxymorphone. Anesthesiology1985;62(2):124–9.

9. Kam PC, Tan KH. Pruritus–itching for a cause and relief?Anaesthesia 1996;51(12):1133–8.

10. Stander S, Gunzer M, Metze D, Luger T, Steinhoff M.Localization of mu-opioid receptor 1A on sensory nervefibers in human skin. Regul Pept 2002;110(1):75–83.

11. Jinks SL, Carstens E. Superficial dorsal horn neuronsidentified by intracutaneous histamine: chemonociceptiveresponses and modulation by morphine. J Neurophysiol2000;84(2):616–27.

12. Chaney MA. Side effects of intrathecal and epidural opioids.Can J Anaesth 1995;42(10):891–903.

13. Thomas DA, Williams GM, Iwata K, Kenshalo Jr DR, Dubner R.Multiple effects of morphine on facial scratching inmonkeys. Anesth Analg 1993;77(5):933–5.

14. Thomas DA, Williams GM, Iwata K, Kenshalo Jr DR, Dubner R.The medullary dorsal horn. A site of action of morphine inproducing facial scratching in monkeys. Anesthesiology1993;79(3):548–54.

15. Metze D, Reimann S, Szepfalusi Z, Bohle B, Kraft D, LugerTA. Persistent pruritus after hydroxyethyl starch infusiontherapy: a result of long-term storage in cutaneous nerves.Br J Dermatol 1997;136(4):553–9.

16. Milkiewicz P, Elias E, Williamson C, Weaver J. Obstetriccholestasis. BMJ 2002;324(7330):123–4.

17. Ballantyne JC, Loach AB, Carr DB. Itching after epidural andspinal opiates. Pain 1988;33(2):149–60.

18. Saravanan S, Robinson AP, Qayoum Dar A, Columb MO, LyonsGR. Minimum dose of intrathecal diamorphine required toprevent intraoperative supplementation of spinal anaesthe-sia for Caesarean section. Br J Anaesth 2003;91(3):368–72.

19. Harvey RP, Wegs J, et al. A controlled trial of therapy inchronic urticaria. J Allergy Clin Immunol 1981;68(4):262–6.

20. Baker RA, Zeller RA, Klein RL, Thornton RJ, Shuber JH,Marshall RE, et al. Burn wound itch control using H1 and H2

antagonists. J Burn Care Rehabil 2001;22(4):263–8.21. Cepeda MS, Alvarez H, Morales O, Carr DB. Addition of

ultralow dose naloxone to postoperative morphine PCA:unchanged analgesia and opioid requirement but decreasedincidence of opioid side effects. Pain 2004;107(1–2):41–6.

22. Sartain JB, Barry JJ, Richardson CA, Branagan HC. Effect ofcombining naloxone and morphine for intravenous patient-controlled analgesia. Anesthesiology 2003;99(1):148–51.

23. Jeon Y, Hwang J, Kang J, Han S, Rhee K, Oh Y. Effects ofepidural naloxone on pruritus induced by epidural morphine:a randomized controlled trial. Int J Obstet Anesth 2005;14(1):22–5.

24. Okutomi T, Saito M, Mochizuki J, Amano K. Prophylacticepidural naloxone reduces the incidence and severity of

neuraxial fentanyl-induced pruritus during labour anal-gesia in primiparous parturients. Can J Anaesth 2003;50(9):961–2.

25. Davies GG, From R. A blinded study using nalbuphine forprevention of pruritus induced by epidural fentanyl.Anesthesiology 1988;69(5):763–5.

26. Lawhorn CD, McNitt JD, Fibuch EE, Joyce JT, Leadley Jr RJ.Epidural morphine with butorphanol for postoperativeanalgesia after cesarean delivery. Anesth Analg 1991;72(1):53–7.

27. Cohen S, Amar D, Pantuck CB, Pantuck EJ, Weissman AM,Landa S, et al. Epidural patient-controlled analgesia aftercesarean section: buprenorphine-0.015% bupivacaine withepinephrine versus fentanyl-0.015% bupivacaine with andwithout epinephrine. Anesth Analg 1992;74(2):226–30.

28. Zylicz Z, Stork N, Krajnik M. Severe pruritus of cholestasis indisseminated cancer: developing a rational treatmentstrategy. A case report. J Pain Symptom Manage 2005;29(1):100–3.

29. Juby LD, Wong VS, Losowsky MS. Buprenorphine and hepaticpruritus. Br J Clin Pract 1994;48(6):331.

30. Iatrou CA, Dragoumanis CK, Vogiatzaki TD, Vretzakis GI,Simopoulos CE, Dimitriou VK. Prophylactic intravenousondansetron and dolasetron in intrathecal morphine-in-duced pruritus: a randomized, double-blinded, placebo-controlled study. Anesth Analg 2005;101(5):1516–20.

31. Pirat A, Tuncay SF, Torgay A, Candan S, Arslan G.Ondansetron, orally disintegrating tablets versus intrave-nous injection for prevention of intrathecal morphine-induced nausea, vomiting, and pruritus in young males.Anesth Analg 2005;101(5):1330–6.

32. Charuluxananan S, Somboonviboon W, Kyokong O, Nimchar-oendee K. Ondansetron for treatment of intrathecalmorphine-induced pruritus after cesarean delivery. RegAnesth Pain Med 2000;25(5):535–9.

33. Borgeat A, Stirnemann HR. Ondansetron is effective to treatspinal or epidural morphine-induced pruritus. Anesthesiol-ogy 1999;90(2):432–6.

34. Tzeng JI, Chu KS, Ho ST, Cheng KI, Liu KS, Wang JJ.Prophylactic iv ondansetron reduces nausea, vomiting andpruritus following epidural morphine for postoperative paincontrol. Can J Anaesth 2003;50(10):1023–6.

35. Wells J, Paech MJ, Evans SF. Intrathecal fentanyl-inducedpruritus during labour: the effect of prophylactic ondanse-tron. Int J Obstet Anesth 2004;13(1):35–9.

36. Korhonen AM, Valanne JV, Jokela RM, Ravaska P, Korttila K.Ondansetron does not prevent pruritus induced by low-doseintrathecal fentanyl. Acta Anaesthesiol Scand 2003;47(10):1292–7.

37. Gurkan Y, Toker K. Prophylactic ondansetron reduces theincidence of intrathecal fentanyl-induced pruritus. AnesthAnalg 2002;95(6):1763–6.

38. Henry A, Tetzlaff JE, Steckner K. Ondansetron is effective intreatment of pruritus after intrathecal fentanyl. Reg AnesthPain Med 2002;27(5):538–40.

39. Charuluxananan S, Kyokong O, Somboonviboon W, Lertma-harit S, Ngamprasertwong P, Nimcharoendee K. Nalbuphineversus propofol for treatment of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg2001;93(1):162–5.

40. Grattidge P. Nausea and vomiting after major arthroplastywith spinal anaesthesia including morphine: a randomisedtrial of subhypnotic propofol infusion as prophylaxis. ActaAnaesthesiol Scand 1998;42(1):124–7.

41. Beilin Y, Bernstein HH, Zucker-Pinchoff B, Zahn J, ZenzenWJ. Subhypnotic doses of propofol do not relieve pruritus

ARTICLE IN PRESS

Pruritus and anaesthesia 91

induced by intrathecal morphine after cesarean section.Anesth Analg 1998;86(2):310–3.

42. Warwick JP, Kearns CF, Scott WE. The effect of subhypnoticdoses of propofol on the incidence of pruritus afterintrathecal morphine for caesarean section. Anaesthesia1997;52(3):270–5.

43. Torn K, Tuominen M, Tarkkila P, Lindgren L. Effects of sub-hypnotic doses of propofol on the side effects of intrathecalmorphine. Br J Anaesth 1994;73(3):411–2.

44. Borgeat A, Wilder-Smith OH, Saiah M, Rifat K. Subhypnoticdoses of propofol relieve pruritus induced by epiduraland intrathecal morphine. Anesthesiology 1992;76(4):510–2.

45. Saiah M, Borgeat A, Wilder-Smith OH, Rifat K, Suter PM.Epidural-morphine-induced pruritus: propofol versus nalox-one. Anesth Analg 1994;78(6):1110–3.

46. Horta ML, Vianna PT. Effect of intravenous alizapride onspinal morphine-induced pruritus. Br J Anaesth 2003;91(2):287–9.

47. Horta ML, Faria CM, Nunes AI, Papaleo TK. Influencia dametoclopramida sobre o prurido provocado pela morfinasubaracnoidea. Rev Bras Anesthesiol 2000;50(Suppl 25):CBA034A.

48. Kjellberg F, Tramer MR. Pharmacological control of opioid-induced pruritus: a quantitative systematic review ofrandomized trials. Eur J Anaesthesiol 2001;18(6):346–57.