Lethal Analgesic Dyad – Opioids + (Benzodiazepines or Gabapentin)

Opioids and benzodiazepines are increasingly used alone or in combination. However, the combined use of these agents increases the risk for potentially lethal respiratory depression.

Gabapentin is a drug often used together with opioids to treat chronic pain, and both have been shown to suppress breathing with worsening complications rates in combination.

General

·      In 2019, 16% of overdose deaths involving opioids also involved benzodiazepines

·      Every day, more than 136 Americans die after overdosing on opioids

·      From 1996 and 2013, benzodiazepine prescription increased by 67%, from 8.1 million to 13.5 million

·      Many people are prescribed both drugs simultaneously

·      In 2016, the Centers for Disease Control and Prevention (CDC) issued new guidelines for the prescribing of opioids. They recommend that clinicians avoid prescribing benzodiazepines concurrently with opioids whenever possible

·      Both prescription opioids and benzodiazepines now carry FDA "black box" warnings on the label highlighting the dangers of using these drugs together

Pathophysiology:

·      Opioids act on the opioid receptor, most prominently the µ-opioid receptor, is associated with the analgesic, respiratory depressant and rewarding effects of opioids

·      Opioids’ main effect is a reduction in respiratory rate which is caused by its direct inhibitory effects on mu receptors in the brainstem

·      Benzodiazepines are agonists of the GABAa receptor and predominantly bind the a1 and a2 subunits of this receptor, inhibiting neuronal signal transmission

·      Benzodiazepine respiratory depression is primarily characterized by a reduction in tidal volume

·      The affinity of the various types of benzodiazepines to the alpha units on the GABAa receptor determines their predominant clinical effect (i.e., sedation or anxiolysis).

·      Both benzodiazepines and opioids reduce upper airway patency and cause obstructive apneas and hypopneas

Interesting Article

This article focused on 29 manuscripts written regarding opioid and benzo interactions and separated manuscripts reviewed based on the clinical context: abuse and addiction, palliative healthcare, inpatient healthcare, and ambulatory healthcare

Abuse and Addiction

·      13 manuscripts identified.

·      The use of opioids with benzodiazepines or other centrally acting drugs has increased over the years

·      This drug combination increases the risk for mortality significantly. 

·      Interestingly, patients on methadone replacement therapy may be at higher risk for mortality and severe adverse respiratory events when concomitantly using benzodiazepines, than patients on buprenorphine replacement therapy

Palliative Healthcare

·      1 manuscript identified

·      This study found that survival in terminally ill patients was not reduced by concomitant use of an opioid with a benzodiazepine or antipsychotic

·      In fact, the chance of surviving longer in this setting was higher

·      May be safe in this context, however additional research is needed to corroborate these results

Inpatient Healthcare

·      3 manuscripts identified

·      They concluded that combined use of opioids and sedatives are likely to increase the risk for in hospital cardiopulmonary and respiratory adverse events and postoperative mortality

Ambulatory Healthcare

·      12 manuscripts identified

·      Looked at a variety of subpopulations including those who are receiving opioids and benzos for chronic non cancer related pain, cancer pain, psychiatric disorders, end stage COPD, and HIV

·      Data suggests that the combined use of opioids and benzodiazepines increases the risk for mortality among a variety of subpopulations

Opioids + Gabapentin

·      Gabapentin is a drug often used together with opioids to treat chronic pain, and both drugs have been shown to suppress breathing, which can be fatal

·      Concomitant opioid use can also increase the amount of gabapentin absorbed by the body, potentially leading to higher risks when these drugs are used together

·      When used together there was an association of 49% increased risk of dying from an opioid overdose

Tips:

·      Be mindful of the medications you are prescribing to your patients

·      Please look on DrFirst and or obtain a list of current medications that patient is taking.

·      Opioids + Benzos can lead to a potentially lethal respiratory depression

·      Be aware that Opioids and Gabapentin have a similar dangerous interaction causing respiratory suppression and death.

·      Make sure the patient has adequate follow up and consider alternative types of analgesia for patients with chronic pain.

References:

https://apm.amegroups.com/article/view/35734/29319

https://nida.nih.gov/drug-topics/opioids/benzodiazepines-opioids

https://www.bmj.com/content/356/bmj.j1224

https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNMattersArticles/downloads/SE19011.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626029/

Galea Lacerations

Anatomy:

 The galea is a dense white layer that covers the periosteum of the skull. It serves as an insertion point for the frontalis and occipitalis muscles

Five layers of the scalp

·      SCALP

o   Skin

o   Dense Connective tissue

o   Aponeurosis (galea)

o   Loose connective tissue

o   Periosteum

Dense connective tissue layer is richly vascularized. The tight adhesion of these vessels to the connective tissue inhibits effective vasoconstriction, hence the large amount of bleeding in scalp lacerations.

The loose connective tissue layer = the DANGER ZONE when lacerated. This layer contains the emissary veins, which connect with the intracranial venous sinuses. Lacerations at this layer are high risk for spreading infection to the meninges!

Approach:

·      Examine the wound, clear of debris, and assess the depth of the wound.

o   Superficial wounds generally don’t gape

o   Deep wounds gape widely due to laceration of aponeurosis, and the tension from the frontalis muscle and occipitalis muscle pull the wound open in opposite directions

·      Hair removal unnecessary unless it interferes with actual closure or knot tying. No increased risk of infection if you do not remove the hair. Shaving head increases risk for infection!

·      Obtain hemostasis with pressure and lidocaine with epinephrine.

·      If the galea is lacerated more than 0.5 cm it should be repaired with 3-0 or 4-0 absorbable sutures. to prevent a serious cosmetic deformity from developing.

·      Skin can be repaired using staples; interrupted, mattress, or running sutures, such as 3-0 or 4-0 nylon sutures; or the hair apposition technique. Removal of sutures or staples in 14 days.

·      Antibiotics - With open skull fractures (blunt or penetrating), should give antibiotics: Ceftriaxone 2 grams q12hr + vancomycin for 24 hours.

Complications:

·      Asymmetric contraction of the frontalis muscle

·      Osteomyelitis, brain abscess - Failure to repair can also allow bacteria to get to the loose connective tissue layer more easily between the galea and periosteum, leading to increased risk of infection

·      Subgaleal hematoma

References:

https://sjrhem.ca/rcp-scalp-lacerations-you-can-leave-your-hat-on/

http://pemsource.org/2019/01/01/question-trauma-10/

https://aneskey.com/special-anatomic-sites/

https://www.aafp.org/afp/2017/0515/p628.html

https://www.vumc.org/trauma-and-scc/sites/default/files/public_files/Protocols/Antibiotics%20in%20CranioFacial%20Trauma%202021.pdf

Tintinallis Emergency Medicine a Comprehensive Study Guide 8th Edition

EMS Protocol of the Week - Excited Delirium (Adult and Pediatric)

Ever wonder why the occasional crew would look to give a whopping 10mg IM midazolam to the curmudgeonly, 50-pound grandma?

Historically, the only protocol that has allowed for sedative medications to be given to facilitate transport has been that for excited delirium, which by definition is supposed to be the hypermetabolic state in which the patient that is presenting an acute risk to self or others; there has not been a protocol for the simply agitated, uncooperative patient. That is still the case now, but in instances of dangerously aggressive geriatrics and pediatrics, there is now a greater shift to weight-base dosing when administering these meds. This has been an overarching change to many of the updated protocols this year, and it means that while the young, large, violent adult may still get the appropriate 10mg IM midazolam by Standing Order, the old, tiny, violent nana might only get 5mg, or less. Time will tell, but hopefully this leads to fewer instances of oversedation, without a large increase in OLMC calls requesting additional meds.

Happy sedating! www.nycremsco.org and the protocol binder for more.

Dave