Journal Club Podcast november 2022

Dr danny marhaba Dr Jiun Kae Pui Professor Peter Cameron

Welcome to the (blated) November Journal Club Podcast. We are again joined by Professor Peter Cameron, Academic Director for the Alfred Emergency and Trauma Centre and Dr Jiun Kae Pui, Emergency Consultant at Alfred Emergency and Trauma Centre.

We will review 3 papers today, covering topics of the efficacy and safety of Paracetamol IV compared to 0.5mg of IV Hydromorphone, Hyperbaric Oxygen for Lower Limb Trauma and aggressive versus moderate fluid resuscitation in patients with acute pancreatitis.

A Randomized Study of Intravenous Hydromorphone Versus Intravenous Acetaminophen for Older Adult Patients with Acute Severe Pain

Read it here
Clinical Question

Is 1g of Paracetamol IV comparable in efficacy and safety to 0.5mg of IV Hydromorphone?

Background

Elderly patients are at risk of undertreatment for pain due to the fear in medication-induced adverse effects and medication interactions. They are more likely to experience delays to analgesia. Intravenous opioids are the mainstay of treatment for severe acute pain in the emergency department. Intravenous paracetamol (APAP / Acetaminophen) also decreases pain without a meaningful rise in adverse effects.

Quote: “It may be that [in a subset of patients] intravenous acetaminophen is sufficiently effective and that intravenous opioids are not warranted.”

Study Design & PICO
Design
 Double Blinded, parallel group RCT among 2 emergency departments in the Montefiore Medical Center in the Bronx, NY.
Population
 Patients aged 65 or more with severe acute pain, onset within the last 7 days, deemed by the attending physician to require intravenous opioid analgesia.
Intervention
 100 mL of normal saline solution, administered as an intravenous drip over 10 minutes, followed by 0.5 mg of intravenous hydromorphone in solution with 2 mL of normal saline solution, administered as a slow intravenous push.
Outcome
 Primary:

  • Difference in Pain on a 0-10 pain scale, measured at baseline and at 60 minutes

Secondary:

  • Requirement for further medication for pain relief at any time
  • Presence of side effects
Findings

By 60 minutes, the patients receiving acetaminophen improved by 3.6 (SD 2.9) on the 0 to 10 pain scale, whereas the patients receiving hydromorphone improved by 4.6 (SD 3.3) (95% CI for the difference of 1.0 was 0.1 to 2.0). 9 medication adverse events were recorded in the hydromorphone group, 5 for the paracetamol group

Authors’ conclusions

“Although the intravenous administration of 0.5 mg hydromorphone was statistically superior to that of 1,000 mg of intravenous acetaminophen for older patients with acute severe pain in the ED, this difference was not clinically important.”

Journal Club thoughts

Initially IV Paracetamol was hampered at our major tertiary centre, in part, due to its cost. In actuality there’s not much difference in affect after 30 minutes between oral and intravenous, but there may be some differences in patients who are vomiting, who have gastrointestinal problems or poor perfusion. Now that the cost of intravenous paracetamol has reduced, it is becoming more reasonable to use for some patient groups.

One challenge with RCT Trials is that they don’t always reflect the reality of how we practice. Emergency department analgesia provision typically involves a multimodal step-wise approach, rather than a single decision point of drug A versus drug B.

An alternative design could include a whole-of-department pathway for pain relief, in a step-wise manner with one of those steps being varied, and outcomes of opioid sparing would be more prominent as a primary outcome.

Bottom Line

Intravenous paracetamol has use in some emergency department patients and is increasingly an option for effective analgesia. However, its use should continue to be within the framework of a stepwise, multimodal approach. Keep using your analgesic ladders, starting from paracetamol (IV or PO) ± NSAIDs, moving onto weak opioids (tramadol / tapentadol), then onto more potent opioids (morphine / oxycodone / hydromorphone), followed by other options for unmanageable pain (ketamine). Use regional blocks where applicable, and don’t forget non-pharmacological options (fracture immobilisation).

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial

Read it here
Clinical Question:

Does adding HBOT to the care of complex open tibial fractures would reduce the rates of acute wound necrosis and/or infection and would this be associated with improved late outcomes?

Background

Hyperbaric Oxygen Treatment (HBOT) is not often used in acute traumatic injury, but has been advocated for. There is suggestion of benefit from animal models and limited randomised trials.

With reference to the Gustillo-Anderson classification, high grade open fractures are high risk for complications like deep infection and delayed union. HBOT offers additional or synergistic anti-infective  effects that may reduce necrosis, oedema and may accelerate healing of bone, nerves and soft tissues.

Study Design & PICO
Design
 Open label, pragmatic randomised trial with blinded outcome arbitration
Population (Target)
 Adult trauma patients with an open tibial fracture within 48 hours from onset of injury, judged by the treating surgeon to be sufficiently severe to carry a high risk of major complications (Included mostly Gustilo Anderson ≥3 with some =2.
Intervention
 12 sessions over 9 days, of pressurisation to 2.4 or 2.8 atm with total oxygen durations of 80-100 minutes each.
Comparison
 Standard Trauma Care
Outcome
 PRIMARY OUTCOME

  • Occurrence of infection and/or necrosis during the period from initial surgery to the 14-day assessment date
  • The Primary Outcome Components were also assessed separately

SECONDARY OUTCOMES

  • Identification of those acute complications that were clinically severe according to a priori guidelines.
What were the findings

Primary Outcome

Primary Outcome
No statistically significant difference between groups in the incidence of the composite primary outcome of one or more acute phase complications (infection and/ or necrosis), with 25 events (43%) in the HBOT group and 34 events (58%) in the control group (odds ratio [OR] 0.55, 95% CI 0.25 to 1.18; P = 0.12).

Primary Outcome Components
Necrosis was reduced in the HBOT group (29% vs 53%;
OR 0.35, 95% CI 0.16 to 0.78; P = 0.01).

    Authors’ conclusions

    This multi-centre randomised trial of HBOT for severe open tibial fractures did not detect a statistically significant reduction in its pre-specified primary outcome measure of the overall number of acute complications of infection and/ or necrosis.

    Journal Club thoughts

    This is methodologically a good study. At the time of planning, all sorts of patients were going through hyperbaric treatments – from athletes to cancer patients to patients with MS.

    The decision to choose a composite outcome introduces risks of the introduction of ‘statistical noise’ – where less overt signs like infection may obscure the overt statistically significant outcomes like necrosis. Had necrosis been chosen as the only primary outcome – this would have been a robustly positive trial. If necrosis can be reduced or prevented in young trauma victims with this intervention – perhaps they should be managed at centres with hyperbaric chambers.

    This is one of the few studies in HBOT that has a robustly positive outcome – despite it not being the pre-specified composite primary outcome. It’s good to have robust evidence for some of the things we already do – this is because it informs and standardises the care we offer patients.

    Bottom Line

    In high grade contaminated tib-fib fractures – trauma teams may consider HBOT as a means to reduce necrosis, once the patient has been stabilised, worked up, and the operating theatre management is complete. In the design of large trauma systems, consideration ought to be given for the availability of HBOT for some trauma patients.

    Paper 3: Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis (WATERFALL Trial)

    Read it here

    Clinical Question

    How does the safety and efficacy of aggressive fluid resuscitation compare with moderate fluid resuscitation in patients with acute pancreatitis?

    Study Design & PICO
    Design
    		 Open Label randomised controlled trial with 1:1 enrolment. Spain, India, Italy, Mexico
    Population
    		 Patients over 18 years of age with acute pancreatitis as defined by the Revised Atlanta Criteria
    Intervention
    		 Aggressive Fluid Resuscitation: Bolus 20 ml/kg, then infusion 3 ml/kg/hr
    Comparison
    		 Moderate Fluid Resuscitation: Infusion 1.5 ml/kg/hr, preceded by bolus 10 ml/kg only if patient has hypovolemia
    Outcomes
    		 Development of moderately severe or severe acute pancreatitis during hospitalisation as per Revised Atlanta Classification
    Findings
    • Stopped early due to harm
    • There was no significant between-group difference in the development of moderately severe or severe acute pancreatitis (22% vs 17%)
    • Safety outcomes of fluid overload 20.5% (aggressive) vs 6.3 (moderate) therefore trial ceased early. p value 0.004

    Authors’ conclusion

    Early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes.

    Journal Club thoughts

    The initial severity of patients with pancreatitis here wasn’t quantified clinically – and to treat a 75kg woman with a 1.5L bolus followed by 1L every 4 hours for 24 hours (6-7L in the first 24 hrs!) without titrating that to urine output, capillary refill, lactate or other measures of intra-vascular volume is not reflective of typical practice.

    There may have been a tendency some decades ago to aggressively fluid resuscitate patients, however it would have been more interesting to compare treatments that clinicians actively use today.

    Bottom Line

    Don’t change your practice – continue to use reasonable fluid resuscitation that are titrated to clinical parameters when treating acute pancreatitis. A 10mL/kg bolus if required followed by a fluid regime that is modified according to urine output, lactate, capillary refill or IVC filling is likely the safest pathway forwards.

    References
    1. C (Kolli S et al. A randomized study of intravenous hydromorphone versus intravenous acetaminophen for older adult patients with acute severe pain. Ann Emerg Med 2022 Nov; 80:432.
    2. Millar IL, Lind FG, Jansson KÅ, Hájek M, Smart DR, Fernandes TD, McGinnes RA, Williamson OD, Miller RK, Martin CA, Gabbe BJ, Myles PS, Cameron PA; HOLLT investigator group. Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial. Diving Hyperb Med. 2022 Sep 30;52(3):164-174. doi: 10.28920/dhm52.3.164-174. PMID: 36100927; PMCID: PMC9536848.
    3. de-Madaria J, Buxbaum JL, Maisonneuve P, et al.Aggressive or moderate fluid resuscitation in acute pancreatitis. N Engl J Med 2022;387:989–1000.
    Dr Dannny Marhaba

    Dr Dannny Marhaba

    Emergency Registrar

    Danny is an Emergency Medicine Registrar at the Emergency and Trauma Centre and the current Senior Registrar for research.
    He trained in regional NSW before moving back to Melbourne to complete his training at the Alfred.