hydromorphone in the financial disclosure ed:...

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HYDROMORPHONE IN THE ED: NECESSARY ANALGESIC OR

UNNECESSARY EVIL?

Sergey M. Motov, MD @painfreeED

FINANCIAL DISCLOSURE

CASE 1 •  75 yom with leg ulcer •  Within 4-hours in ED:

– MS 2 mg IV, HM 2 mg IV x2 doses – Fentanyl patch

•  One hour after last dose: – Patient is unresponsive, bradypneic – Naloxone IV, immediate response

CASE 2 •  65 yom with 7 mm kidney stone •  Over 3-hours in ED:

– HM 4 mg IV x 3 doses

•  Two hours after last dose: – Patient unresponsive – Bradypneic and Bradycardic – IV Naloxone – IV Atropine – Transferred to ICU

CASE 3 •  54 yof with acute pancreatitis

– MS 2 mg IV at 12 pm and 2 pm in the ED – HM 2 mg IVP at 3 pm, 4 pm, and 6 pm

•  At 7 pm: – Patient unresponsive – Bradypneic – Naloxone IV – Transferred to SICU

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CASE 4 •  82 yom with back pain •  Over 5-hours in the ED

– MS 2 mg IVP, HM 2 mg IVP x2 doses

•  On the floor: – Lethargic – Bradycardic – Hypoxic: 80% on RA – Naloxone IV, transferred to ICU

CASE 5 •  22 yom with SCD: painful VOC crisis •  Over 1 ½ hours in the ED

– HM 6 mg IVP x3 doses •  1h after last dose:

– Unresponsive in the bathroom – Pulseless, PEA arrest – Could not be resuscitated

•  Does not provide better analgesia than morphine

•  Does cause pruritus and severe respiratory depression

•  Does accumulate in patients with renal failure

REALITY OF HYDROMORPHONE

•  EM Providers: – Gaps in/lack of understanding hydromorphone efficacy and potency

– Morphinophobic – Hydromorphonophillic

REALITY OF HYDROMORPHONE INTRODUCTION

•  Hydromorphone: – semisynthetic 𝜇-opioid agonist – faster onset, shorter half-life – more potent:

•  1 mg HM=6.7-8.5mg MME •  1.5 mg HM=10 mg MME

– H3G metabolite: renally excreted, neuro-toxic

Gulur et al, 2015

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INTRODUCTION •  Hydromorphone:

– equianalgesic dosing: similar to morphine, no difference in AE

– greater euphoric effects – severe respiratory and CNS depression

Gulur et al, 2015

INTRODUCTION •  Hydromorphone:

– 262% increase in production (2003 to 2013)

– 140% increase in medical use, 438% increase in misuse (2004-2011)

– high likeability, abuse liability and street value

– growing national and international concern regarding it’s use

Gulur 2015, Alturi 2014

•  Morphine use decrease: 69% to 52% •  Hydromorphone use increase: 27% to 43% •  Hydromorphone:

– perceived “safer” than morphine – believed “superior analgesic” – over-prescribed: 1 mg vs. 4 mg of MS

OBJECTIVES •  Is Hydromorphone better analgesic than

Morphine in the ED? •  Are we overdosing Hydromorphone in

the ED? Why? •  Is Hydromorphone really safer in

patients with renal insufficiency? •  How BAD are the side effects of

Hydromorphone?

IS HYDROMORPHONE BETTER ANALGESIC THAN

MORPHINE?

Hydromorphone vs. Morphine

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0.015 mg/kg vs. 0.1 mg/kg

•  Better pain relief at 30 min (∆ 5.5 vs. ∆ 4.1)

•  Less pruritus ( 0% vs. 6%) •  Similar rates of rescue analgesia and

antiemetics



0.0075 mg/kg IV vs. 0.05-mg/kg

•  No difference in pain score at 30 min (3.8 vs. 3.3 NRS)

•  Similar AE, rescue analgesia


JUST A THOUGHT

Why Hydromorphone is not used for Pre-hospital,

Battlefield, and Pediatric analgesia (with exception

of SCD)?

WHY ARE WE OVERDOSING HYDROMORPHONE ?

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EQUIANALGESIC CONVERSION

•  Potency: – Oral:

• 1 mg HM=5-8mg MS (MME) – Intravenous

• 1 mg HM=6.7-8.5mg MS(MME) • 1.5 mg HM=10 mg MS (MME)

Knotkova 2009, Gregory 2013

HYDROMORPHONE DOSING


•  77%-adequate analgesia at 15 min •  96%-adequate analgesia within 1h •  5%-Hypoxia (<95% O2)

1mg IVP + 1mg IVP 15 min later


•  Pain score: 10 to 1 at 5 min; to 0 at 30 min

•  32%: SO2 below 95% •  None received IV naloxone

2 mg IVP


•  Analgesics declined at 30 min: – 77% in HM group, 66% in usual care

•  SE: more pruritus in HM group (18% vs. 9%)

•  Dosing variability: 1 mg MS to 4 mg HM •  Hydromorphone: higher pain score, home

opioid use, drug-seeking behavior, back pain, kidney stone


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• No difference in pain score change between 2 mg MS and 2 mg HM

• Hydromorphone: more antiemetics and more rescue analgesia


•  293 pts, IV Opioid bolus – 75%: 2 mg morphine – 14%: 2 mg hydromorphone – Dosing regimen: prescriber's choice


•  Home use/renal colic: HM •  Provider preference/habit: MS •  HM dose >50% higher then MS •  46%: reasons w/o pharmacologic

validity

HYDROMORPHONE DOSING THE REASON WE OVERPRESCRIBE HYDROMORPHONE

JUST A THOUGHT

Why Morphine (single dose, titration) has not been studied as rigorously as

Hydromorphone in the ED?

IS HYDROMORPHONE SAFE IN PATIENS WITH RENAL

INSUFFICIENCY?

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HYDROMORPHONE AND RENAL FAILURE

•  Renally excreted, accumulates in RF (4 times the level)

•  Neuro-excitation and cognitive impairment •  Lower dose, increased dosing intervals

required

Hydromorphone-3-Glucoronide

HYDROMORPHONE AND RENAL FAILURE

•  Cmax and AUC (0-48h) increased 3-fold in severe RF (CLcr < 30 mL/min)

•  Slow elimination-terminal T1/2 (40 hr) •  Lower dosing and longer intervals are

MUST

HOW BAD ARE HYDROMORPHON’S SIDE

EFFECTS?

HYDROMORPHONE SE

•  17%: abnormal VS during 1-hour protocol •  5%: O2 Sat< 95% at 15 min, 1.2% <90% •  10%: bradycardic •  13% nausea, 7% vomiting

1mg IVP + 1mg IVP 15 min later

HYDROMORPHONE SE

•  32%: SO2 < 95%: •  26%: SO2 90-94% •  6%: SO2 <90% ( lowest 82%)

•  16% nausea, 7% vomiting

2 mg IVP •  “1+1”group”:

– Hypoxia: 22% vs. 5% – Respiratory Depression: 30% vs. 17% – Physician Interventions: 26% vs. 17% – Similar change in pain score

HYDROMORPHONE SE

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HYDROMORPHONE SE

•  73 ADE: 54-Med Errors, 43-patients harm •  Hydromorphone:

– Given to 62% patients, 32%-ADE: •  75%-medication errors •  74%-resulted in harm

HYDROMORPHONE SE •  Hydromorphone:

– Lipophilicity and Potency: • 10 times more lipophilic than MS • Positive psychomimetic effects (euphoria, tranquility and rewarding)

• Recreational use (“high”) • Continued self-administration in a dose-escalating pattern (abuse)

• No data from ED studies on euphoria, reinforcement and abuse liability

HYDROMORPHONE SE EUPHORIA AND REINFORCEMENT: •  Jasinski 1997

– 10 times greater than morphine in opioid-addicted patients

•  Hill 2000 – higher ratings on “having pleasant

bodily sensations” and “liking of the drug” of hydromorphone than morphine

HYDROMORPHONE SE

•  Hydromorphone: – Greater sedation – More euphoria – Higher abuse liability

HYDROMORPHONE SE HYDROMORPHONE SE

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HYDROMORPHONE IN THE ED

•  IS NOT superior to morphine for pain relief

•  IS almost always overdosed •  IS severely euphoric with high abuse

potential •  DOES cause severe respiratory and

CNS depression •  DOES accumulate in patient with RI/

RF

TAKE-HOME MESSAGE

• No evidence to support Hydromorphone use over Morphine in the ED

• HM use should be discouraged • Call for HM removal from ED is

long overdue

hydromorphone in the financial disclosure ed:...

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