AHA Evidence Based Guidelines

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AHA Evidence Based Guidelines

• How to proceed with scant evidence

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Levels of Evidence 1
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Levels of Recommendation
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AHA Guidelines

• Cocaine-Induced Ventricular Dysrhythmias
• Recommended Therapies, Ordered By Preference
• Sodium Bicarbonate (IIB), Lidocaine (IIB), Alpha
  Adrenergic Blockers (IIB)
• Inappropriate Therapies
• Non-Selective Beta Blockers, Epinephrine (Both
  III)
• Cocaine-Induced Acute Coronary Syndrome (ACS)
• Recommended Therapies, Ordered by Preference
• Benzodiazepines (IIB), Nitrates (IIB),
  Alpha-Adrenergic Antagonists (IIB)
• Inappropriate Therapies
• Non-Selective Beta-Blockers (III)

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AHA Guidelines

• Calcium Channel Blocker Poisoning or Overdose
• Recommended Therapies, Ordered By Preference
• Pacemaker, Vasopressors, High-Dose If
  Necessary(IIB), Calcium (IIB)
• Beta-Blocker Poisoning or Overdose
• Recommended Therapies, Ordered By Preference
• Pacemaker, Vasopressors, High-Dose If Necessary
  (IIB), Glucagon (IIB)

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AHA Guidelines

• Tricyclic Antidepressant Poisonings
• Recommended Therapies, Ordered By Preference
• Sodium Bicarbonate (IIB), Lidocaine
• Inappropriate Therapies
• Procainamide (III)
• Refractory Drug-Induced Shock
• High-Dose Vasopressors (IIB), Circulatory Assist
  Devices (IIB), Vasopressin (Indeterminate)

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Opiate Poisoning Ventilation before Naloxone?

• Dr Andrew Dawson
• Director Hunter Area Toxicology Service
• Newcastle, Australia

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Opiate Poisoning Ventilation before Naloxone?

• Evidence supports the correction of respiratory
  failure with bag valve mask techniques followed
  by administration of naloxone in any patient
  suspected of opioid induced respiratory failure.

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Are all clinical situations the same?

• 24 year male recreational heroin OD
• 75 year male IHD post operative narcosis
• 24 year old post heroin OD respiratory arrest
  being ventilated

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Naloxone Ventilation Grid
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Naloxone Efficacy

• Animal
• Good controlled studies
• Clinical data
• Anaesthetic
• Good controlled studies
• Clinical Toxicology
• Case series
• indirectly address the issues

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Naloxone Risk

• Incidence of possible ADR lt1
• Seizure cardiac arrest
• Extremely rare
• Probably catecholamine mediated
• ? Pulmonary Oedema
• Behavioural 7

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Naloxone Catecholamines

• Increases catecholamine release
• especially in the presence of hypercapnoea
• The correction of of hypercapnoea reduces
  haemodynamic effects.
• Mills CA (1988)
• There is no clinical evidence to support
  hypercapnoea correction prior to administration
  of naloxone.

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Mills et al
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Mills et al
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Naloxone Dose

• 0.12 mg endpoint ETCO2 lt 6.5
• Tigerstedt
• Out of Hospital Protocol Driven

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Respiratory Arrest/Depression

• Detectable pulse BP
• gt90 response to naloxone
• IVIM
• Sporer et al
• IVSC
• Wanger et al

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Opioids Asystolic arrest

• Prehospital physician paramedic medical team
  survival (4/7)
• all IV naloxone
• Bertini G et al 1992.
• Prehospital paramedic (0/16)
• 50 received naloxone IV
• Sporer KA et al 1996

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Is Naloxone Neurotoxic?

• Glutamate mediated neuroexcito-toxicity
• Modulating effect of endorphines morphine
• Direct effects of Naloxone

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Excitotoxicity
Excitatory amino acids, glutamate
Increased intracellular calcium and sodium
Ca2
Protein kinases C, II Proteases Phosphatases
Phospholipases Xanthine oxidase
Nitric oxide synthase (NO) Heme oxygenase (CO)
Endonucleases
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Glutamate accumulation
Presynaptic
Postsynaptic
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NMDA
Sodium and Calcium
NMDA or glutamate
Glycine
Zinc
SH
Poly- amine
Phencyclidine
NO-S
H
Magnesium
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AMPA, Kainate
AMPA Kainic acid or glutamate
Sodium or Calcium
2,3-benzo- diazepines
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Drug modification

• Decreased glutamate release
• Adenosine derivatives, catecholamines
• Sodium channel blockers
• Phenytoin
• Lamotrigine
• Ca2-channel blockers (L-type)
• Nimodipine
• Platelet activating factor antagonists

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Drug modification

• Glutamate receptor antagonism
• Glutamate binding site
• 2,3-benzodiazepine site
• GYKI 52466, ? very high dose diazepam
• Glycine binding site
• Felbamate
• Receptor associated ion channel
• Magnesium, ketamine, memantine
• Redox modulatory site
• Nitroglycerine, nitroprusside

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Opioids Ventilation before Naloxone

• Evidence supports efforts to correct respiratory
  acidosis and hypoxia followed by naloxone
  administration in patients suspected of opioid
  induced respiratory failure.
• Class IIb

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Naloxone Dose

• IMI 0.8mg
• If systolic BP gt100 mmHg
• IV 0.4 mg
• Cardiac arrest
• If an IV line is in situ
• Repeated titrated against response
• Rate of non-behavioural adverse reactions does
  not appear to be related to dose