Caudal Ketamine things that have influenced my practice

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Caudal Ketamine things that have influenced my
practice
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Comparison of the effects of adrenaline,
clonidine and ketamine on the duration of caudal
analgesia produced by bupivacaine in children.B
Cook, DJ Grubb, LA Aldridge, E Doyle
(Edinburgh)BJA 1995 75 698 - 701

• Randomised controlled trial, boys 1-10yrs,
  Orchidopexy
• 0.25 Bupivacaine with Adrenaline, Clonidine or
  Ketamine
• Median duration of analgesia
• Ketamine 12.5 hours
• Clonidine 5.8 hours
• Adrenaline 3.2 hours
• No differences in motor block, urinary retention
  or sedation
• Potential for ketamine related neurotoxicity
  discussed but not considered to be a major problem

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Use of caudal-epidural opioids in children still
state of the art or the beginning of the end?PA
Lonnqvist, G Ivani and T Moriarty (Sweden, Italy,
UK)Paediatric Anaesthesia 2002 12 747 749

• Editorial
• Reviewed the history of opioid additives to
  caudal analgesia
• Pointed out some of the major side effects and
  questioned the opioid bandwagon
• Noted the availability of effective alternatives
  (including ketamine) with less distressing/dangero
  us side effects
• Considered single dose preservative free ketamine
  to be safe despite concerns about neurotoxicity.
• Recommended further studies

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Nonopioid additives to local anaesthetics for
caudal blockade in children a systematic
review.M Ansermino, R Basu et al
(Vancouver)Paediatric Anaesthesia 2003 13 561
- 573

• A systematic review of randomised controlled
  trials comparing the use of LA and LA nonopioid
  additives in children
• Ketamine, Clonidine, Midazolam, Adrenaline
• 4 RCTS involving ketamine identified
• Significantly increased duration of analgesia
  with ketamine over other drugs with no increased
  side effect profile
• Concerns regarding neurotoxicity but suggested
  that preservative free formulation (esp S)
  appears safe
• Noted that ketamine is not licenced for
  extradural use
• Further large studies needed to establish safety

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Caudal additives in children solutions or
problems?D de Beer and M Thomas (GOSH)BJA 2003
90 (4) 487 - 498

• Another review article
• Echoed the efficacy and desirable side effect
  profile
• Again considered the question of neurotoxicity
• Is it the preservative or the ketamine that is
  responsible??
• Considered the use of S isomer with similar
  worries
• Not licenced

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Caudal analgesia and anesthesia techniques in
children.B Tsui and C Berde (Edmonton and
Boston)Current Opinion in Anaesthesiology 2005
18 283 - 288

• A review of developments in caudal anaesthesia in
  infants and children
• Noted the efficacy of additives to caudal LA,
  including ketamine ,with lack of side effects
• Raised questions regarding the neurotoxicity
  question but considered single dose preservative
  free S ketamine to be safe
• controversial animal studies and apoptotic
  neurodegeneration
• Lack of availability of preservative free
  ketamine (including UK) likely to be a barrier to
  use

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Severe Toxic Damage to the Rabbit Spinal Cord
after Intrathecal Administration of
Preservative-free S Ketamine.JH Vranken, D
Troost et al (Amsterdam)Anesthesiology 2006
105 813 - 818

• Repeated daily (7 days) intrathecal
  administration of preservative free S ketamine
  vs. saline in rabbits
• Post mortem examination of spinal cord and nerve
  roots showed lesions suggestive of toxic damage
  in 11 of 12 ketamine treated group
• No changes observed in 5 control animals
• No difference in neurologic status between the 2
  groups after 7 days of treatment, but some
  temporary motor impairment in some ketamine
  treated animals soon after injection
• Concluded that repeated administration of a
  clinically relevant dose has a toxic effect on
  the rabbit CNS

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A survey of paediatric caudal extradural
anesthesia practice.R Menzies, K Congreve et al
(Oxford)Pediatric Anesthesia 2009 19 829 - 836

• An online survey of APAGBI members
  (international) in 2008
• Examined many aspects of caudal extradural
  practice
• 366 responses
• Commonly used additives clonidine (42) and
  ketamine (37.5)
• Clonidine more popular despite evidence that
  ketamine leads to a greater prolongation of
  block.
• Suggested this may be due to difficulty sourcing
  preservative free solution and/or concerns
  regarding neurotoxicity
• (Other interesting things regarding needle
  technique and skin decontamination protocols)

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Intrathecal ketamine in the neonatal rat spinal
toxicity, apoptosis and long term functional
outcome.BD Westin, S Walker et al (international
research group)Oral presentation, APA Annual
Scientific Meeting, May 2010

• An investigation of analgesic efficiency, spinal
  cord toxicity and long term outcome following
  intrathecal ketamine in the neonatal rat
• Single dose lumbar intrathecal ketamine in 3, 7
  and 21 day old rats
• Ketamine dose dependently reversed hyperalgesia.
  Apoptosis varied with post natal age and was
  increased by ketamine in 3 day old rats. This was
  associated with microglial activation and altered
  spinal function
• Acute pathology and long term behavioural change
  occured in the same dose range as analgesic
  effects. The therapeutic ratio of ketamine is
  less than 1 in the neonatal rat

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So what will I do now?

• Ketamine is an effective agent for prolonging the
  analgesic effects of caudal extradural blockade
• It has an attractive adverse effect profile when
  compared with some other agents
• There have, for a long time, been concerns about
  its potential neurotoxicity but these have not
  been well understood
• Yet it remains a popular agent with practicing
  anaesthetists
• More recent animal studies do appear to indicate
  real concerns about the potential for ketamine to
  cause neurotoxic effects in the developing spinal
  cord
• I think Im going to give it up