Emergency Medical Symposium

Clinical Pearl 70 : Push Dose Nitroglycerin (PDN)

65 year old male with severe respiratory distress.

Initial impression presents an obese 65 year old male with gross respiratory distress, tripod, audible rales and with one word sentences, pale, diaphoretic and anxious. High flow nasal cannula underneath a CPAP mask with 10 cmH2O of PEEP is placed. Initial vital signs of RR 36 ppm, HR 118, irregular, BP 210/108, SpO2 93 % on 100% oxygen.

Primary survey is as above, GCS 15, no focal neurological deficits, unremarkable skin inspection, no s/s of trauma. SAMPLE history significant for increasing DOE with orthopnea and PND x 2 weeks, worse today. NKDA, Metformin, coreg, ASA, Lipitor, Glipizide, amlodipine, lasix and plavix. CAD s/p PCI with stents, AFib, DM2, hypercholesterolemia, HTN

12 lead ECG narrow-complex Afib with RVR @ 120 bpm, lateral T-wave inversion. Repeat VS unchanged. 

So what’s our next step…CPAP, IV Access, and maybe Lasix in select cases.  Nitroglycerin for preload reduction… Tabs, spray or paste is not going to work; leaves nitroglycerin infusion. NTG Infusions have been effective, depending on how aggressive the dosing schedule, nitro can rapidly reduce the blood pressure and after load.

KEY FACTS:

•    Standard NTG Infusion concentration is 200 mcg/mL; 50mg of Nitroglycerin in 250 mL of D5W either pre-mixed in a glass infusion vial or mixed at the beside.

•    Nitro infusions can be given using the 3/10 rule. Every 3 mL/hr is equal to 10 mcg/min of NTG infusion. For example: 50 mcg/min is 15 mL/hr infusion (3 x 5=15), 200 mcg/min is 60 ml/hr (3 x 20=60), 400 mcg/min is 120 mL/hr infusion (3 X 40=120).

•    Every 2 mL of Nitro Infusion is 400 mcg, equal to one SL tablet or spray pump.

•    If 1 tablet or 2mL bolus is given every 5 minutes, this equals 80 mcg/min.

•    Sublingual administration is very similar to IV infusion in bioavailability and time of onset.

•    Leave the pump in the cabinet and give 1 mL to 2 mL of the standard NTG Solution every minute, 200-400 mcg/min, titrated to effect.

•    Using a 10 fold dilution of the concentrated vial can be used as a Push Dose Nitro Solution. 5 mg (1 mL of the concentrated NTG Vial) mixed with 9 mL of Saline is 500 mcg/mL. Give 1 mL or 500 mcg every 60-90 seconds to lower the blood pressure.

Nitroglycerin lowers preload via venous vasodilation at low doses and lowers after load via arterial vasodilation at high doses, this makes our vascular container larger lowering the systemic pressure. Aggressive, high dose NTG paired with the recruitment of the alveoli using CPAP & PEEP make up the mainstay of pre-hospital treatment of APE and decompensated heart failure. Bolus doses as high as 2 mg (2000 mcg) of nitroglycerin have been given safely and effectively in previous studies.

In emergent resuscitations we need to focus on bolus dose medications in the acute phase versus starting and titrating critical care infusions while a patient is in extremis. The goal is to achieve clinical end points of treatment faster with bolus dosing at the bedside and then begin maintenance infusions once resuscitation goals are met and the hemodynamics are stable.

Stay tuned for a protocol

References:

Hsiao, R, et al. “Contemporary Treatment of Acute Heart Failure”. Progress in Cardiovascular Diseases. 2016;58:367-378.

Scott, MC & Winters, ME. “Congestive Heart Failure”. Emerg Med Clin N Am. 2015;33:553–562.

Mattu, A & Lawner B. “Prehospital Management of Congestive Heart Failure” Heart Failure Clin. 2009;5:19–24.

Weingart, S. “Sympathetic Crashing Acute Pulmonary Edema” EMCrit Podcast #1, 2009. http://emcrit.org/podcasts/scape

Levy, P; et al. “Treatment of Severe Decompensated Heart Failure With High-Dose Intravenous Nitroglycerin: A Feasibility and Outcome Analysis”. Ann Emerg Med. 2007;50:144-152.

Zalenski, RJ; et al. “The Feasibility of Treating Severe Acute Congestive Heart Failure With Bolus Intravenous Nitroglycerin”Ann Emerg Med. 2004;44.

Use of Beta-Blockers to Treat Patients with Ventricular Fibrillation

Ventricular fibrillation (VF) is the presenting cardiac rhythm in up to 40% of out-of hospital cardiac arrests. VF that does not respond to the first few defibrillation attempts is associated with high morality rates of up to 97%. ACLS guidelines recommend treating cardiac arrest patients with refractory VF with epinephrine, and amiodarone or lidocaine.  However these guidelines are often unsuccessful in achieving and maintaining return of spontaneous circulation (ROSC). Although not part of ACLS guidelines, some literature supports considering double sequence defibrillation as well as administering beta-blockers for VF refractory after standard ACLS protocol has been initiated.

Mechanism:

 

Refractory ventricular fibrillation is a severe form of electrical storm, defined as a clustering of destabilizing episodes of VF in a short period of time that does not respond to multiple defibrillation attempts. Cardiac arrest patients have high levels of catecholamines due to endogenous release and exogenous administration of epinephrine. Beneficial effects of these catecholamines are seen in the activation in of a1 receptors which cause vasoconstriction and increased coronary perfusion pressure. Adverse effects of epinephrine are seen through the activation of b1 and b2 receptors, which increase myocardial oxygen demand, worsen ischemic injury, lower VF threshold, and worsening post-resuscitation myocardial function. The use of beta-blockers is predicted to help terminate electrical storm and help prevent patients from re-entering into VF.

Evidence:

 

A small retrospective study (n=25) performed by Driver et al. (2014) demonstrated that the use of esmolol in refractory VF given after receiving at least three unsuccessful attempts at defibrillation, epinephrine 3 mg, and amiodarone 300mg. Esmolol was administered in a 500 mcg/kg bolus and followed by a drip of 0-100mcg/kg/min. Results showed that administration of esmolol was associated with higher rates of temporary ROSC, sustained ROSC, survival to hospital discharge, and discharge with favorable neurologic outcomes. Beta-blockers in refractory VF have been studied in animal and human models since the 1960’s. Though the existing literature supports a beneficial effect of beta-blockade in patients with VF/VT, high quality human trials are still lacking. Most studies have been evaluating the utility of propranolol or esmolol.

Interestingly, the ARREST and ALIVE trials showed that while amiodarone is associated with increased survival to hospital admission, it was not associated with a survival to discharge. However, in Driver et al. (2014) esmolol was associated with a survival benefit.

Conclusion:

 

            Beta-blockade should be considered in patients with refractory VF prior to the cessation of resuscitative efforts. 

References:

1.         Bourque, Daniel et al. B-Blockers for the treatment of cardiac arrest from ventricular fibrillation. Resuscitation 2007; 75:434-444.

2.        Carvalho de Oliveira, Felipe et al. Use of beta blockers for the treatement of cariac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: A systemic review. Resuscitation 2012; 83: 674-683.

3.        Driver, Brian et al. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation 2014; 85: 1337-1341.

Pediatric PAIN Management… No IV… No Problem... Think Intranasal (IN) Fentanyl or Ketamine

Clinical Pearl 69

Background

·         Intranasal pain control is as effective as intravenous (IV) pain control.

·         Ease of delivery / Rapid delivery (If you do not have a preexisting IV catheter in place).

·         Painless administration, no “shot” needed.

·         Can be titrated, may repeat ½ to full dose every 10-15 minutes.

Indications for Pre Hospital Use

·         Pain control prior to starting an IV.

·         Painful procedure.

·         Burns.

·         Orthopedic Trauma, Suspected fracture.

Contraindications

·         Nasal Trauma, Septal abnormalities or Obstruction (copious mucous, bleeding, anatomic obstruction or foreign body)

Drugs and Dosing (NOT equivalent to IV dosing)

·         Fentanyl  2 mcg/kg (Max dose 100mcg)

·         Most common concentration is 50 mcg/mL, 5mcg = 0.1mL

·         Ex: 25kg child. 25 kg x 2 mcg/kg = 50 mcg.

·         Draw up 1mL (50mcg) + 0.1mL (estimated dead space) = 1.1mL. Spray 1 spray in each nostril, alternating nostrils, for 4 sprays.

·         Ketamine 1mg/kg (Max dose 10mg)

Tips

·         Minimize volume (large volumes are lost in the pharynx or out of the nostril).

·         Maximize concentration. Do NOT dilute.

·         Blood and mucus should be suctioned if possible prior to administration.

·         Neck extended in sitting position delivers medication higher onto the nasal turbinates to enhance absorption and nose brain transport.

·         If you fail to use adequate dosing then you will fail to achieve adequate effect.

·         There is often a “dead space” within the delivery device, consider drawing up that extra volume into the syringe to account for the dead space that will remain, approximately 0.1mL of dead space. This may vary depending on type of device you are using.

·         0.2 to 0.3mL per nostril is ideal, may push up to 1mL per nostril if needed but there will be some drug loss.

·         Use BOTH nostrils for volumes over 0.3mL. If you need more than 2mL total (3-4 sprays in each nostril), consider titration with a second dose in 5 minutes.

Effect

·         It will take minutes to absorb and begin achieving therapeutic effect in 3-5 minutes but peaking at 10-15 minutes.

·         Use of vasoconstrictors might reduce drug absorption (cocaine, epinephrine, oxymetazoline, phenyephrine).

Side Effects

·         Respiratory depression is rare, except in sufentanil and high concentrated patented nasal formula of fentanyl, 400mcg/spray. IN medications given in proper doses will rarely achieve levels high enough to cause clinically important respiratory depression due to the delay in rise of serum concentration.

·         Use of vasoconstrictors might reduce drug absorption (cocaine, epinephrine, oxymetazoline, phenyephrine).

·         Does not burn. IN medications are tolerated well.

Reversal: Naloxone IN or IV for opioids.

Conclusion: Pediatric Pain... No IV... No Problem... Think Intranasal (IN)

References

1.      Borland, A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department, Ann Emerg Med, 2007.

2.      Goldman, Intranasal drug delivery in children, Curr Drug Therapy, 2006.

3.      Graudins, A., R. Meek, et al. The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Ann Emerg Med, 2015.

4.      Intranasal.net

5.      Reid, C., R. Hatton, et al. Case report: prehospital use of intranasal ketamine for pediatric burn injury. Emerg Med J, 2011.

6.      Rickard, A randomized controlled trial of intranasal fentanyl vs. intravenous morphine for analgesia in the prehospital setting, 2007. 

7.      UpToDate, Lexicomp. Fentanyl and Ketamine Drug Information.

8.      Wolfe, Intranasal Medications in EMS, JEMS 2003.

9.      Wolfe and Braude, Intranasal medication delivery for children: A brief review and update. Pediatrics 2010.

10.  Yeaman, F., E. Oakley, et al. Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: A pilot study. Emerg Med Australas, 2013.