Analgesia en Pediatra AINEs y Paracetamol

Ximena Figueroa Y. Junio 2013

Introduccin

Encuestas en los aos 1970s-1980s informaban que lactantes y nios reciban menos analgesia postoperatoria que los adultos. Algunos neonatos eran operados con mnimos niveles de anestesia, aunque esta prctica recibi algunas crticas.

Berde C, Sethna N. Analgesics for the Treatment of Pain in Children. N Engl J Med 347 (14): 1094-1103, 2002.

Introduccin
El dolor debe anticiparse y prevenirse en todas las edades. La Academia Americana de Pediatra promueve la utilizacin de mtodos efectivos para el alivio del dolor. Una aproximacin utilizando analgesia multimodal: anestesia regional, opiodes, AINES y paracetamol est ampliamente aceptado.

Jhr M. Postoperative pain management in infants and children: new developments. Curr Opin Anaesthesiol 13: 285-289, 2000.

Desarrollo de la Nocicepcin
RN 26 semanas de gestacin: Vas aferentes de dolor perifricas, espinales y supraespinales desarrolladas Comportamientos especcos y signos autonmicos, hormonales y metablicos de estrs en relacin a dao tisular. El desarrollo de vas inhibitorias descendentes ocurre posterior al desarrollo de vas aferentes. Algunos estudios muestran que el dolor no tratado en neonatos genera consecuencias prolongadas en el comportamiento.

Berde C, Sethna N. Analgesics for the Treatment of Pain in Children. N Engl J Med 347 (14): 1094-1103, 2002.

Berde C, Sethna N. Analgesics for the Treatment of Pain in Children. N Engl J Med 347 (14): 1094-1103, 2002.

Paracetamol

Paracetamol
Inhibidor dbil de prostaglandinas en tejidos perifricos No posee efectos antiinamatorios importantes Droga de accin central Reduce la liberacin central de PGE2 No inhibe Ciclooxigenasa perifrica: baja toxicidad renal y gastrointestinal

Jhr M. Postoperative pain management in infants and children: new developments. Curr Opin Anaesthesiol 13: 285-289, 2000.

Mecanismos de accin
Mecanismos de accin alternativos propuestos: Inhibicin de la va L-arginina-NO mediada por sustancia P o NMDA Refuerzo de las vas descendentes inhibitorias serotoninrgicas Efecto sobre receptores canabinoides.

Anderson B. Paracetamol (Acetaminophen): mechanisms of action. Pediatric Anesthesia 18: 915-921, 2008.

Farmacocintica
Absorcin por va oral se relaciona con la velocidad de vaciamiento gstrico, concentraciones mximas 30-60 min. Se ja levemente a las protenas plasmticas. Metabolismo por sistema microsomal heptico a sulfato de acetaminofn y glucornido (inactivos) Vida media 2-3 hrs, relativamente no se afecta con la funcin renal. Absorcin oral disminuida en el neonato.

Katzung B. Farmacologa Bsica y Clnica. Pag. 670,1120. Editorial El Manual Moderno, Mxico DF, 1996.

Paracetamol oral

30 semanas gestacin: 25 mg/Kg/da 34 semanas: 45 mg/Kg/da oral Trmino: 60 mg/Kg/da 6 meses: 90 mg/Kg/da

Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003

Paracetamol rectal

Va rectal: Se recomiendan dosis de carga 35-45 mg/Kg En prematuros: 20 mg/Kg pero con intervalos mayores a 8 hrs para prevenir un aumento progresivo en las concentraciones plasmticas.

Jhr M. Postoperative pain management in infants and children: new developments. Curr Opin Anaesthesiol 13: 285-289, 2000.

nd nhe he al al al kg as er ain he or

From Korpela et al. [14..], with permission.

Paracetamol

Rectal acetaminophen, mg/kg

Table 1. Guidelines for paracetamol dosing for analgesia in healthy children according to Morton and Arana [19 . .] Oral Rectal Maintenance Maximum Duration initial initial dose oral/ Dosing daily dose at dose dose rectal interval (mg/kg/ maximum (mg/kg) (mg/kg) (mg/kg) (h) day) dose (h) 20 20 20 20 20 40 15 15 15 12 8 46 60 60 90 48 48 72

Age group Preterm 03 months 43 months

ng a . ].

pain, and are clearly more effective than paracetamol. Jhr M. Postoperative pain management in infants and children: new developments. Curr Opin Anaesthesiol 13: This has not yet been as clearly demonstrated for the 285-289, 2000.

Paracetamol ev
En Australasia: Neonatos <10 das: 7,5 mg/Kg c/6 hrs Neonatos >10 das-nios hasta 33 Kg: 15 mg/kg c/6 hrs En Europa: No est rotulado para uso en <10 das Neonatos >10 das -lactantes 10 Kg: 7,5 mg/kg c/6hrs Nios 10-40 Kg: 15 mg/kg c/6 hrs (mx 60 mg/kg/da)

Anderson B, Allegaert K. Intravenous neonatal paracetamol dosing: the magic of 10 days. Pediatric Anesthesia 19: 289-295, 2009.

Paracetamol ev
Dosis variable: 20 mg/Kg/da en prematuros <31 sem gestacin 40 mg/Kg/da en neonatos >37 semanas. Palmer et al: 28-32 sem gestacin: 10 mg/Kg c/6 hrs 32-36 sem: 12,5 mg/kg >36 sem: 15 mg/Kg

Anderson B, Allegaert K. Intravenous neonatal paracetamol dosing: the magic of 10 days. Pediatric Anesthesia 19: 289-295, 2009.

Paracetamol ev

1000 mg/100 ml: nios >33 Kg 500 mg/50 ml: nios <33 Kg Administracin por perfusin en aprox 15 min, con intervalo al menos 4 hrs. (Fresenius Kabi)

Paracetamol: seguridad
Hepatotoxicidad: Balance entre produccin N-acetyl-p-benzoquinoina-imina (NAPQI) por el citocromo P450 (CYP) Estrs oxidativo En neonatos: No hay mediciones de concentracin de paracetamol y produccin de NAPQI No hay mediciones de CYP2E1

Anderson B, Allegaert K. Intravenous neonatal paracetamol dosing: the magic of 10 days. Pediatric Anesthesia 19: 289-295, 2009.

Paracetamol: seguridad
Hepatotoxicidad neonatal y encefalopata en neonato de 5 das que recibi 3 das de paracetamol 156 mg/Kg/da el primer da y luego 78 mg/Kg/da. Nios que recibieron dosis de paracetamol repatidas >90 mg/kg/da pueden presentar anormalidades en la funcin heptica. Estudios en voluntarios sanos evidencian elevacin de GPT hasta 3 veces despus de 1 semana de tratamiento con paracetamol con o sin opiodes v/s placebo. Hepatotoxicidad dosis >150 mg/Kg

Anderson B, Allegaert K. Intravenous neonatal paracetamol dosing: the magic of 10 days. Pediatric Anesthesia 19: 289-295, 2009.

AINEs

Drogas efectivas para tratamiento de dolor leve a moderado en nios. Efecto analgsico, antipirtico y antiinamatorio. Combinacin con paracetamol produce mejor analgesia que cada uno por separado.

Analgesia Review. Pediatric Anesthesia 2008, 18 (Suppl. 1) 64-78

Phospholipids
Inhibited by steroids

Phospholipase A2 Arachidonic acid + lysophospholipids

Inhibited by NSAIDs

Cyclooxygenase PGG2 Peroxidase

PGF2 reductase

PGH2
PGI2 synthetase

TXA2 synthetase

PGE2 synthetase

PGF2

PGE2

PGI2

TXA2

Figure 1 Schematic diagram of arachidonic acid metabolism.

Anderson B. Paracetamol (Acetaminophen): mechanisms of action. Pediatric Anesthesia 18: 915-921, 2008.

and e inuen stricto platele PGs i pediat and an tion o manag Muc inhibit and an the ar not ha does i Parace periph

ed mechanisms of action. The two known isoforms of COX (COX-1 and COX-2) convert arachidonic acid to the unstable intermediate prostaglandin H. The synthesis of prostaglandin H is the point of differentiation in prostanoid production, with individual cell types possessing predominantly different terminal synthases. The terminal synthases generate the effector prostaglandins. Although COX-1 and COX-2 govern the maximum production of prostaglandins, acute changes in production are regulated proximally by activation of phospholipase A2. The ability of different NSAIDs to differentially inhibit COX-1 and COX-2 has been well studied.[4] Structural differences in the two COX isozymes permit selective inhibition.[5] mucosa, platelet aggregation, maintenance of glomerular filtration rate (GFR), vascular homeostasis, and macrophage differentiation. In contrast, COX-2 is primarily constitutively expressed, or continuously induced, in the kidney and brain, but is induced in areas of injury. COX-2 mRNA expression also changes during organogenesis and in the newborn period, particularly in the intestine, lung, and kidney.[7] COX-2 induction is inhibited by glucocorticoids.[6] COX-2 expression in the brain increases after seizure activity and N-methyl-D-aspartate (NMDA) stimulus. In the kidney, COX-2 expression is increased by salt restriction. COX-2 is also important developmentally in the kidney; gene knockout mice for COX-2 have had severe renal abnormalities.[8,9] COX-2 is also

COX y desarrollo fetal

Table I. Cyclo-oxygenase (COX)-1 and COX-2 messenger RNA (mRNA) changes during human fetal development (reproduced from Olson et al.,[7] with permission from Elsevier Science) Organ Lung Intestine Kidney COX isoform COX-1 COX-2 COX-1 COX-2 COX-1 COX-2 First trimester ++++ + ++ + +++ 0 Second trimester +++ ++ +++ ++ +++ + Third trimester ++ +++ ++ ++++ +++ ++ Neonate + ++++ +++ +++ +++ ++++

+, ++, +++, ++++ = relative abundance of mRNA within each organ.

Adis Data Information BV 2003. All rights reserved. Pediatr Drugs 2003; 5 (6)

Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003

Preparaciones, dosis y vas de administracin

Ibuprofeno: tableta, jarabe, tableta dispersable sublingual. Diclofenaco: tableta (dispersable y con recubrimiento entrico), supositorio, frmulas parenterales. Ketorolaco: iv Naproxeno: tabletas orales Ketofrofeno: tabletas orales, jarabe, frmulas parenterales. Reportes de uso de inhibidores COX-2 selectivos en nios igual ecacia que AINEs no selectivos. Tendran menor riesgo de hemorragia digestiva.

Analgesia Review. Pediatric Anesthesia 2008, 18 (Suppl. 1) 64-78

Ibuprofeno

No recomendado en neonatos para manejo del dolor o ebre. Para DAP: 10 mg/Kg/dosis c/24 hrs por 3 das. No hay evidencia que sustente la administracin en neonatos UK: uso licenciado en >7Kg

Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003 Eustace N. Use of nonsteroidal anti-inammatory drugs in infants. Pediatric Anesthesia 2007 17: 464-469, 2007.

Ketorolaco
Mezcla racmica 1:1 enantimeros R(+) y S(-). Farmacocintica estudiada en 10 nios entre 4-8 aos que recibieron dosis 0,5 mg/kg despus de una ciruga menor. No hay datos farmacocinticos disponibles en neonatos. Dosis recomendada para manejo del dolor en Infants 0,5 mg/Kg ev c/8 hrs o infusin 0,17 mg/kg/hr, ambos hasta 2 das.

Anderson B. Comparing the efcacy of NSAIDs and paracetamol in children. Pediatric Anesthesia 14: 201-217, 2004. Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003

Diclofenaco

Farmacocintica estudiada en nios 4-6 aos con dosis 0,5 mg/Kg iv. No hay datos farmacocinticos en neonatos. Dosis analgsica postoperatoria: 1 mg/Kg rectal c/12 hrs. UK: Uso licenciado para nios >1 ao

Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003 Eustace N. Use of nonsteroidal anti-inammatory drugs in infants. Pediatric Anesthesia 2007 17: 464-469, 2007.

Ketoprofeno

No hay datos farmacocinticos disponibles en neonatos. Dosis 0,5-1 mg/kg c/8 hrs Recomendado para nios entre 3 meses hasta 14 aos.

Morris J. Nonsteroidal Anti-inammatory Agents in Neonates. Pedriatr Drugs 5: 385-405, 2003

Analgesia Review. Pediatric Anesthesia 2008, 18 (Suppl. 1) 64-78

Toxicidad y efectos adversos

Reacciones de hipersensibilidad Disminucin de la agregacin plaquetaria Inhibicin de la funcin renal mediada por PG. Ibuprofeno reduce la tasa de ltracin glomerular en un 20% en neonatos Pueden causar gastritis y hemorragia digestiva. Poco riesgo en uso post operatorio limitado a 1-3 das. Ibuprofeno menor irritacin gstrica. Piroxicam, ketorolaco, ketoprofeno mayor propensin a efectos adversos GI en la vejez.

Analgesia Review. Pediatric Anesthesia 2008, 18 (Suppl. 1) 64-78

Dipirona
Pertenece grupo AINEs Activacin va NO-GMPc-canales K+ lo que lleva a hiperpolarizacin neurona y desensibilizacin. Posiblemente relajacin de msculo liso por esta va: efecto antiespasmdico. SNC: inhibicin sntesis PG , activacin vas inhibitorias descendentes y sistemas opiodrgicos.

Concenso grupo de expertos mexicanos. Ecacia y seguridad del metamizol.Gac Med Mex 140 (1): 99-101, 2004.

Dipirona: seguridad
Inhibicin PG principalmente a nivel central, menor dao gastrointestinal. Disminucin de la PA con administracin en bolo por vasodilatacin secundaria a activacin va NO-GMPc- canales K+. Metamizol y su metabolito activo MAA no afectan diferenciacin de los granulocitos ni inducen apoptosis de los ya diferenciados. Agranulocitosis: origen inmunoalrgico, incidencia 1,2 casos/1.000.000 personas expuestas por 1 semana.

Concenso grupo de expertos mexicanos. Ecacia y seguridad del metamizol.Gac Med Mex 140 (1): 99-101, 2004.

Uso de AINEs en UK
Pediatric Anesthesia 2007 17: 464469 doi:10.1111/j.1460-9592.2007.02135.x

Use of nonsteroidal anti-inammatory drugs in infants. A survey of members of the Association of Paediatric Anaesthetists of Great Britain and Ireland
NICHOLAS EUSTACE
FFARCSI DCH MRCPI FCARCSI MMEDSCI,

BRENDAN OHARE

Department of Anaesthesia and Critical Care Medicine, Our Ladys Hospital for Sick Children, Crumlin, Dublin, Ireland

Summary
Background: Nonsteroidal anti-inammatory drugs (NSAIDs) are commonly used as perioperative analgesics. Many are currently used off label. Diclofenac is currently licensed for use in children over 1 year of age for the treatment of juvenile rheumatoid arthritis, while

Uso de AINES en UK
Encuesta por correo enviada a todos los miembros de la Asociacin de Anestesistas Peditricos de Gran Bretaa e Irlanda con carta explicativa. 418 encuestas enviadas, 337 contestadas (80,6%), 23 respondedores estaban retirados. 86% utilizaban AINEs en su prctica clnica habitual.

% responde

% re

50 40 30 20 10

42.9

Ibuprofen Others

20

AINEs perioperatorio
5.7 11.5 9.8 0 1.3 1.3 Intraoperative Postoperative ICU

10

Figure 3 Dosage i

0.3

466

N . EU S T A C E A N D B. O H A R E
Figure 1 Perioperative nonsteroidal anti-inammatory drug use in infants.

90 80 70
% responders

60 90

78.6

% responders % responders

73.6

50 80 40 70 30 60 20 50 10 40 0

81.5

80.6

(1.3%) use NS for ade used b (5.6%)

60 50 40 30 20 10 0 5.7 1.3 1.3 Postoperative 42.9

Discu
Oral Rectal Intravenous
6 hourly 8 hourly 12 hourly 18 hourly

Diclofenac Ibuprofen Others

30

11.5 9.8 0.3 ICU

Figure 3 20 Dosage interval when prescribing diclofenac.

10 0 Oral Rectal

9.2

Intraoperative

Figure 1 Perioperative nonsteroidal anti-inammatory drug use in infants.

90 80 70

81.5

80.6

(1.3%) (Figure 3). Fifty-seven per cent of responders Figure 2 use NSAIDs as a component of the analgesic regime Route of administration of nonsteroidal anti-inammatory drugs. for adenotonsillectomies; diclofenac in particular is used by 44% of members. NAIDs are used by 19 (5.6% ) members in ICU following cardiac surgery. by 4% of responders; 13 months by 19 %; 4 6 months by 48%; 612 months by 78% and 90% prescribe them in children >1 year of age (Table 1). Discussion The most commonly prescribed dose of diclofenac

Intravenous

The pr widely paucity used in subject more l 80% re therefo membe with p rates o William effect o the pr Associa Britain admini

Prescripcin en <1 ao
Table 1 Cumulative nonsteroidal anti-inammatory drug prescription patterns in infants by APA members <1 month 3.8% 13 months 19.4% 46 months 47.7% 612 months 78% >1 year 90.4%

6 months by 48%; 612 months by 78% and 90% prescribe them in children >1 year of age (Table 1). The most commonly prescribed dose of diclofenac )1 )1 )1 is 1 mgkg (59%); 2 mgkg (19%) and 3 mgkg (1.3%). The interval between doses prescribed varies between 6 (3.5%), 8 (53%) 12 (11%) and 18 hourly

Associat Britain adminis Some m Our s consensu enac do (1 mgkg Based on a higher are acce recomm children prescrib

Journal compilation 2007 Bla

A Meta-Analysis of the Use of Nonsteroidal Society for Pediatric Anesthesia Antiinammatory Drugs for Pediatric Postoperative Pain Section Editor: Peter J. Davis

A Meta-Analysis of the Use of Nonsteroidal Antiinammatory Drugs for Pediatric Postoperative Pain
Daphne Michelet, MD, Juliette Andreu-Gallien, MD, PhD, Tarik Bensalah, MD, Julie Hilly, MD, Chantal Wood, MD, Yves Nivoche, MD, PhD, Jean Mantz, MD, PhD, and Souhayl Dahmani, MD, PhD
BACKGROUND: Opioid side effects are a great concern during the postoperative period in children. Nonsteroidal antiinammatory drugs (NSAIDs) have been shown to effectively decrease postoperative pain, but their opioid-sparing effect is still controversial. In this present metaanalysis, we investigated the postoperative opioid-sparing effect of NSAIDs in children. METHODS: A comprehensive literature search was conducted to identify clinical trials using NSAIDs and opioids as perioperative analgesic compounds in children and infants. Outcomes measured were opioid consumption, pain intensity, postoperative nausea and vomiting (PONV), and urinary retention. All outcomes were studied during postanesthesia care unit (PACU) stay and the rst 24 postoperative hours. Data from each trial were combined to calculate the pooled odds ratios (ORs) or standardized mean difference (SMD) and their 95% condence interval. RESULTS: Twenty-seven randomized controlled studies were analyzed. Perioperative administration of NSAIDs decreased postoperative opioid requirement (both in the PACU and during the rst 24 postoperative hours; SMD 0.66 [0.84, 0.48] and 0.83 [1.11, 0.55], respectively), pain intensity in the PACU (SMD 0.85 [1.24, 0.47]), and PONV during the rst 24 postoperative hours (OR 0.75 [0.57 0.99]). NSAIDs did not decrease pain intensity during the rst 24 postoperative hours (OR 0.56 [0.26 1.2]) and PONV during PACU stay (OR 1.02 BACKGROUND: Opioid side effects are a great concern during the postoperative period in [0.731.44]). Subgroup analysis according to the timing of NSAID administration (intraoperative versus postoperative), type of surgery, or coadministration of paracetamol did not show any children. Nonsteroidal antiinammatory drugs (NSAIDs) have been shown to effectively decrease inuence of these factors on the studied outcomes except the reduction of pain intensity and the postoperative pain, but their opioid-sparing effect is still controversial. In this present metaincidence of PONV during the rst 24 postoperative hours, which were inuenced by the coadministration paracetamol and the type of surgery, respectively. analysis, we of investigated the postoperative opioid-sparing effect of NSAIDs in children. CONCLUSION: This meta-analysis shows that perioperative NSAID administration reduces METHODS: A comprehensive literature period search was (Anesth conducted opioid consumption and PONV during the postoperative in children. Analg to identify clinical trials using 2012;114:393406) NSAIDs and opioids as perioperative analgesic compounds in children and infants. Outcomes

Daphne Michelet, MD, Juliette Andreu-Gallien, MD, PhD, Tarik Bensalah, MD, Julie Hilly, MD, Chantal Wood, MD, Yves Nivoche, MD, PhD, Jean Mantz, MD, PhD, and Souhayl Dahmani, MD, PhD

measured were opioid consumption, pain intensity, postoperative nausea and vomiting (PONV), effects such as nausea andduring postoperative urinary retention. care unit (PACU) stay espite preventive strategies against All opioid side and urinary retention. outcomes were studied postanesthesia To decrease the incidence of such undesirable effects, the effects, including postoperative nausea and vomitand the rst 24 postoperative hours. Data from each trial were combined to calculate the pooled authors concluded that it is necessary to use balanced ing (PONV), respiratory depression, urinary retenodds and ratios (ORs) oradverse standardized meanwhen difference and their 95% condence interval. analgesia morphine is(SMD) used. tion, constipation, pruritus, these events NSAIDs have been shown to improve postoperative remain a great concern in the postoperative period and a RESULTS: Twenty-seven randomized controlled studies were analyzed. Perioperative administrapain both in adult and pediatric populations. However, major source of discomfort for patients. tion of NSAIDs decreased postoperative opioid effects requirement in the PACU and during the rst the opioid-sparing of NSAIDs (both in children and inMany adult studies have shown non-opioid analgesics fants are still the subject of debate. In addition, it is still 24 postoperative hours; SMD 0.66 [ 0.84, 0.48] and 0.83 [ 1.11, 0.55], respecsuch as ketamine, nonsteroidal antiinflammatory drugs unclear whether combined administration of opioids and (NSAIDs), acetaminophen, and nefopam to exhibit an opioidtively), pain intensity in the PACU (SMD 0.85 [1.24, 0.47]), and PONV during the rst 24 NSAIDs improves postoperative pain relief in children. sparing effect and improve postoperative analgesia quality. postoperative hours (OR 0.75 [0.57 0.99]). did not decrease pain intensity during the Meta-analysis of NSAIDs published studies is a statistical methA qualitative meta-analysis addressed the efficacy of odology allowing aggregation and quantification of the rst 24 postoperative (OR 0.56 [0.26 1.2]) and PONV during PACU stay (OR 1.02 postoperative morphine in children. Among hours its findings, therapeutic effects from multiple studies. It is particularly morphine was only effective whenSubgroup compared withanalysis a control [0.731.44]). according to conflicting the timing of arise NSAID (intraoperative interesting when results from administration multiple therapy. Moreover, it was associated with significant side studies. The goal of the present was to versus postoperative), type of surgery, orprimary coadministration ofstudy paracetamol did not show any investigate the efficacy of balanced analgesia using NSAIDs inuence of these on the studied outcomes except the reduction of pain intensity and the From the Department of Anesthesia, Intensive Carefactors and Pain Management, and opioids for the management of postoperative pain in Robert Debre University Hospital, Paris Diderot University, Paris Sorbonne incidence of PONV during the rst 24 postoperative which were inuenced by the children with a special emphasis hours, on both the quality of Cite , Paris, France. postoperative analgesia and the opioid-sparing effects of Accepted for publication October 3, 2011. coadministration of paracetamol and the type of surgery, respectively. NSAIDs. The authors declare no conflicts of interest. CONCLUSION: This meta-analysis shows that perioperative NSAID administration reduces Reprints will not be available from the authors. Address correspondence to Souhayl Dahmani, MD, PhD, Department of opioid consumption and PONV during the postoperative period in children. (Anesth Analg Anesthesia, Intensive Care and Pain Management, Robert Debre University METHODS Hospital, Paris Diderot University, Paris Sorbonne Cite , 48 Blvd. Se rurier, 2012;114:393406) Bibliographical Search and Analysis

4,6,7

2 6

75019 Paris, France. Address e-mail to souhayl.dahmani@rdb.aphp.fr. Copyright 2012 International Anesthesia Research Society
DOI: 10.1213/ANE.0b013e31823d0b45

espite preventive strategies against opioid side effects, including postoperative nausea and vomiting (PONV), respiratory depression, urinary retention, constipation, and pruritus, these adverse events remain a great concern in the postoperative period and a major source of discomfort for patients.1
February 2012 Volume 114 Number 2

We conducted this meta-analysis according to the guidelines of the Cochrane Handbook for Systematic Reviews of
www.anesthesia-analgesia.org

effects such as nausea and postoperative urinary retention. 393 To decrease the incidence of such undesirable effects, the authors concluded that it is necessary to use balanced analgesia when morphine is used. NSAIDs have been shown to improve postoperative pain both in adult and pediatric populations.4,6,7 However,

ity of Reporting of Metal guidelines on this statis-

n 2 literature databases: wing queries were used: en or infant. The names Ds: diclofenac, dexibupron, ibuprofen, ketoprofen, c acid, meloxicam, nabunoxicam, tiaprofenic acid, ugs (celecoxib, etoricoxib, , valdecoxib). In addition, es found in the selected meta-analyses) was also t recent search was April physicians to verify their ive opioid therapy in both l group without NSAID d the potential risk of bias experts13: randomization description of the method mine whether intervention reseen in advance of, or d study, incomplete data ut excluded patients and e reporting (absence of tudies were excluded if ent, if anesthesia and/or tandardized, and if the exhibit at least one of the history of gastroduode-

Figure 1. Meta-analysis owchart. RTC randomized controlled trial.

decrease in PONV, urinary retention, or pruritus risk, whereas a 95% confidence interval of the SMD 0 indicates significantly adequate pain control or an opioid dose-sparing effect. Concerning the common cutoff values considered for SMD, the effect of the NSAIDs on the

Requerimientos de opiodes

Figure 2. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative opioid requirement during postanesthesia care unit stay. The square in front of each study (rst author and year of publication) is the standardized mean difference (SMD) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled SMD with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Figure 2. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative opioid requirement during postanesthesia care unit stay. The square in front of each study (rst author and year of publication) is the standardized mean difference (SMD) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled SMD with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Intensidad del dolor

Figure 3. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative pain intensity during postanesthesia care unit stay. The square in front of each study (rst author and year of publication) is the standardized mean difference (SMD) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled SMD with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

February 2012 Volume 114 Number 2

www.anesthesia-analgesia.org

399

Figure 4. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative opioid requirement during the rst 24 hours. The square in front of each study (rst author and year of publication) is the standardized mean difference (SMD) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled SMD with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Intensidad del dolor

Figure 5. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative pain intensity during the rst 24 hours. The square in front of each study (rst author and year of publication) is the standardized mean difference (SMD) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled SMD with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

against postoperative urinary retention (4 studies; OR 0.96 [0.253.65]; I2 49%, P 0.12) or pruritus (3 studies;

modify this result (Table 3). However, when including the 2 studies in which paracetamol was systematically

Nuseas y vmitos

Figure 6. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative nausea or vomiting during postanesthesia care unit stay. The square in front of each study (rst author and year of publication) is the odds ratio (OR) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled OR with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Nuseas y vmitos
Figure 6. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative nausea or vomiting during postanesthesia care unit stay. The square in front of each study (rst author and year of publication) is the odds ratio (OR) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled OR with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Figure 7. Forest plot of meta-analysis of the effects of perioperative nonsteroidal antiinammatory drugs (NSAIDs) on postoperative nausea or vomiting during the rst 24 hours. The square in front of each study (rst author and year of publication) is the odds ratio (OR) for individual trials, and the corresponding horizontal line is the 95% condence interval (CI). The lozenge back in the gure is the pooled OR with the 95% CI. Studies with 1 intervention group are shown with asterisks (Author, year of publication* and Author, year of publication**).

Analysis found a significant publication bias for the fol-

Kendall 0.11, P 0.58; or Eggers test: bias 2.79, P

Analgesia preventiva
Editorial

Perioperative Analgesia: What Do We Still Know?

urrent clinical practices designed to minimize pain in the perioperative period should be based on scientific evidence from the peer-reviewed Henrik Kehlet, MD, PhD medical literature.1 The recent and unprecedented retraction of 21 peerreviewed articles and abstracts published by Dr. Scott S. Reuben, a leading Spencer Liu, MD investigator in the perioperative use of nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors, raises important questions as to the potential adverse impact of Dr. Reubens fraudulent work on the practice of acute (perioperative) pain management. The purpose of this editorial is to provide a brief overview of the status of the field, distinguishing our understandings that remain fully supported from those that are no longer supported by the unimpeached literature. The classical NSAIDs and the newer COX-2 drugs have been reported to provide effective postoperative analgesia and opioid-sparing effects after a wide variety of both in- and outpatient surgical procedures by numerous International Anesthesia Research Society Vol 108, (5): 1364-1367, 2009 investigative groups around the world. In one of their retracted articles
Paul F. White, PhD, MD*

Continuar...