In the United States of America, acute pain, and the expectation of pain management is one of the primary reasons that prehospital providers receive calls.  By definition from the International Association for the Study of Pain, "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage." As such, pain or the perception of pain can have both physiological and psychological impact on patients that interferes with their activities of daily living, causes a delay in healing and recovery and ultimately impacting the quality of life of the patient.[1][2] Based upon NEMSIS v2, 33.1% of the complaints to 911 are for pain-related syndromes with chest pain accounting for 10.2% of all calls.[3][4] The most common provider impression based upon this 2016 data includes traumatic injuries at 21.8%, abdominal pain at 12.2%, and chest pain at 10%.  This data means that almost half of all provider impressions are dealing with some form of a pain-related syndrome.  A similar study looking at the national electronic prehospital patient records of 41,241 patients transported by EMS providers in Denmark showed a 28% moderate or severe pain level with an additional 32% of unknown pain status.[5]  Galinski et al. in the prevalence and management of acute pain in the prehospital emergency medicine, indicated that 42% of the individuals having acute pain with 64% of those patients having intense to severe pain.[6] The National Association of EMS Physicians (NAEMSP) believes that relieving pain and suffering of patients is of necessity a priority for every emergency medical services (EMS) system. The 2018 EMS Scope of Practice Model looked at pain management for acute traumatic events as a high priority issue requiring a systematic review of the literature. 

Prehospital providers have to perform appropriate pain assessment and understand options for the treatment of acute pain.  Pain assessment and treatment can be difficult based upon several different factors, including patient's age, race, location, EMS provider's ability or reluctance to administer pain medication, and the medical director's authority on the administration of pain medication.  There is also a growing concern that the administration of opiate or opioid medication will cause addiction and abuse. One of the major hurdles for pain medication administration in the United States before 2014 was that prehospital providers would use standing orders to administer controlled substances for pain control. This administration of pain medication was based upon the 1970 Controlled Substances Act with an interpretation that EMS providers were allowed to administer pain medication under the DEA registration of the medical director or hospital system. The DEA rejected standing orders for controlled substances for prehospital providers.  Congress passed the Protecting Patient Access to Emergency Medications Act of 2017, which modified the Controlled Substances Act of 1970 to allow for EMS agencies to be registered with the DEA and use standing orders. The Act also gives specific instructions on the storage of controlled substances, provides for the restocking of EMS vehicles at hospitals, requires maintenance of controlled substance records, and holds EMS agency liable for controlled substances. 

The 2003 position paper from NAEMSP believes that every EMS protocol should have (8) components: (1) mandatory assessment of both the presence and severity of pain, (2) use of reliable tools for the assessment of pain, (3) indications and contraindications for prehospital pain management, (4) non-pharmacologic interventions for pain management, (5) pharmacologic interventions for pain management, (6) mandatory patient monitoring and documentation before and after analgesic administration, (7) transferal of relevant patient care information to receiving medical personnel and (8) quality improvement and close medical oversight to ensure appropriate use of prehospital pain management.[7] The Declaration of Montreal from the International Pain Summit indicates that the relief of pain is a global issue and that healthcare providers, including the prehospital providers, have a humanitarian responsibility to provide access and management of pain.[8]  

The problem at hand for most prehospital providers deals with the ability to perform an appropriate pain assessment and then deciding which analgesia to use for the perceived pain. The measurement of pain and relief of pain is a complex entity with limited literature on education, research, agent availability, state and federal regulations on controlled substances, and the perception of pain based upon race, age, gender, and cultural beliefs. [9] Porter et al. (1999) and Johnston et al. (1997) show that neonates undergoing painful procedures in the NICU rarely received analgesic agents (6.8% and 10% respectively) with the literature showing that early pain experiences can have long-term sequela to the patients.[10][11] Lord et al. concluded that there is no difference between genders receiving analgesia, but did indicate that there is a difference between the types of medication given.[12] Perception of acute pain assessment and providing analgesia from paramedics shows that children and adolescents continue to receive fewer analgesic interventions compared to adults.[13] Prehospital pain management has evolved over the years, and education on pain management has improved. In a six-year follow-up study, the knowledge, perceptions, and management of pain by paramedics from an urban/suburban fire department showed improvement for treating pain based upon the quality improvement program and educational interventions.[14]  

Pain Assessment Tools

The use of validated pain assessment tools is an integral part of the assessment and treatment of patients with acute pain. Prehospital healthcare protocols or guidelines should include specific validated tools based upon the patient type to include age and ability to communicate.[15] There are several different pain scales based upon age that ranges from preterm to adulthood. Srouji et al. have listed over 20 different pain scales for preterm to 18 years of age.[11] Additional scales include those for the non-verbal patients as well as those with dementia. The measurement of pain and pain intensity can be performed by several methods, which include: behavioral, physiological measures, and self-reporting. The most widely used pain assessment scales utilize the self-reporting method, which has the most valid and optimal measurements, but these scales are limited in the pediatric population because of the cognitive and language development of children and lack of the younger child's ability to describe the pain.[11] These scales also have limited utility for the non-verbal patient because of the inability to vocalize. Pain assessment for the younger patient, as well as the non-verbal patient is then based upon the behavioral and physiological measurements.  Body posture and movements, crying, and facial expressions are examples of behavioral measures. Physiological measures would include key vital signs of heart rate, blood pressure, respiration, and oxygen saturation, as well as palmer sweating and other neuroendocrine responses.[11] Some popular tools include:

• NIPS Scale (Neonatal Infant Pain Scale) [16]
  • Used in children less than one (1) year of age. 
  • Adapted from the CHEOPS scale and composed of six (6) indicators:
    • Facial expression
      • Score 0: Relaxed
      • Score 1: Grimace
    • Crying
      • Score 0: No Cry
      • Score 1: Whimper
      • Score 2: Vigorous crying
    • Breathing patterns
      • Score 0: Relaxed
      • Score 1: Change in breathing
    • Arms
      • Score 0: Restrained
      • Score 0: Relaxed
      • Score 1: Flexed
      • Score 1: Extended
    • Legs
      • Score 0: Restrained
      • Score 0: Relaxed
      • Score 1: Flexed
      • Score 1: Extended
    • State of arousal
      • Score 0: Sleeping
      • Score 0: Awake
      • Score 1: Fussy
  • Pain Level
    • 0 - 2 = No Pain to Mild Pain; No intervention
    • 3 - 6 = Moderate Pain; Non-pharmacological intervention with a reassessment in 30 minutes
    • 7 - 10 = Severe Pain; Non-pharmacological intervention and possibly a pharmacological intervention with a reassessment in 30 minutes
• FLACC Scale (Face, Legs, Activity, Cry, Consolability) [17] 
  • For children between the ages of two months and seven years. It can also be useful for individuals who are unable to communicate their pain, such as intubated adult patients in the intensive-care unit.[18]
  • The calculation of the total score is by adding the individual (5) criteria together for a resulting score from 0 to 10
  • Figure 1 for evaluation / download
    •  Face
      • Score 0: No facial expression or smile
      • Score 1: Occasionally grimaces or frowns; appears withdrawn, disinterested
      • Score 2: Frequently or constantly quivering chin, clenched jaw
    •  Legs
      • Score 0: Normal position or relaxed
      • Score 1: Uneasy, restless, or tense
      • Score 2: Kicking or legs drawn up
    •  Activity
      • Score 0: Lies quietly in a normal position and moves easily
      • Score 1: Squirms or shifts back and forth, tense
      • Score 2: Arched, rigid or jerking
    •  Cry
      • Score 0: No crying (awake or asleep)
      • Score 1: Moaning or whimpering; occasional complaining
      • Score 2: Steady crying, screaming or sobbing, frequent complaining
    •  Consolability
      • Score 0: Content and relaxed
      • Score 1: Distractable, reassured by occasional touching, hugging or being talked to
      • Score 2: Difficult to console
  • Pain Level
    • 0 = No Pain
    • 1 - 3 = Mild Pain
    • 4 - 6 = Moderate Pain
    • 7 - 10 = Severe Pain
• Wong-Baker FACES Pain Rating Scale [19]
  • Originally created for children to help them communicate about their pain, it is now used for patients ages 3 to 18 years of age. This scale can be used with individuals that are impaired. The patient chooses from a series of faces that correlate to a numerical value.
  • Scale
    • Smiling (0) - No hurt
    • Partial smile (2) - Hurts a little bit
    • Neutral (4) - Hurts little more
    • Slight frown (6) - Hurts even more
    • Frowning (8) - Hours a whole lot
    • Crying (10) - Hurts worst
• Numeric Pain Rating Scale (NRS Pain) [20]
  • One of the primary methods of patient pain assessment where the patient either circles or verbalizes the whole number (0 - 10 integers) corresponding to their pain intensity where (0) is no pain and (10) is extreme pain. There has been high test-retest reliability and validation for acute pain for this scale reported in both literate and illiterate patients.
  • Pain Level
    • 0 = No Pain
    • 1 - 3 = Mild Pain; Nagging, annoying, interfering little with ADLs, person's ability to concentrate or think
    • 4 - 6 = Moderate Pain; Interferes significantly with ADLs, person's ability to concentrate or think
    • 7 - 10 = Severe Pain; Disabling, unable to perform ADLs, person's ability to concentrate or think
• Nonverbal Pain Scale (NVPS) for Nonverbal patients [1]
  • Combination of behavioral and physiologic measurement for assessment of the non-verbal patient
    • Face
      • Score 0: No particular expression or smile
      • Score 1: Occasional grimace, tearing, frowning, wrinkled forehead
      • Score 2: Frequent grimace, tearing, frowning, wrinkled forehead
    • Activity (movement)
      • Score 0: Lying quietly, normal position
      • Score 1: Seeking attention through movement or slow, cautious movement
      • Score 2: Restless, excessive activity and/or withdrawal reflexes
    • Guarding
      • Score 0: Lying quietly, no positioning of hands over areas of the body
      • Score 1: Splinting areas of the body, tense
      • Score 2: Rigid, stiff
    • Physiology (vital signs)
      • Score 0: Baseline vital signs unchanged
      • Score 1: Changes in SBP > 20 mmHg or HR > 20 beats / minute
      • Score 2: Changes in SBP > 30 mmHg or HR > 25 beats / minute
    • Respiratory
      • Score 0: Baseline RR / SpO2 synchronous with ventilator
      • Score 1: RR > 10 breaths / minute over baseline, 5% decrease SpO2 or mild ventilator asynchrony
      • Score 2: RR > 20 breaths / minute over baseline, 10% decrease SpO2 or severe ventilator asynchrony
  • Pain Scores
    • 0 - 2 = No Pain to Mild Pain
    • 3 - 6 = Moderate Pain; Consider analgesia. Sepsis, hypovolemia, and hypoxia need to be resolved prior to interventions
    • 7 - 10 = Severe Pain; Consider analgesia. Sepsis, hypovolemia, and hypoxia need to be resolved prior to interventions
• Pain Assessment in Advanced Dementia (PAINAD)
  • Warden, Hurley, and Volicer developed this scale that is similar to the FLACC scale but uses the 0 - 10 pain scale. 
  • The PAINED scale uses breathing, negative vocalization, facial expression, body language, and consolability as the criterion for pain
  • Figure 1 for evaluation / download
  • Pain Scores
    • 0 = No Pain
    • 1 - 3 = Mild Pain
    • 4 - 6 = Moderate Pain
    • 7 - 10 = Severe Pain

Pain Management

Prehospital pain management can occur via the non-pharmacologic and pharmacologic means.  Pak et al. performed a review of the literature for non-pharmacological interventions for pain management, which includes: distraction, stress management, hypnosis, acupuncture, acupressure, transcutaneous electrical nerve stimulation, and physical therapies (including massage, heat/cold, physiotherapy, osteopathy, and chiropractic).[21] Additional treatment options for newborn and infant children include repositioning, singing or soft music, rocking the child, swaddling, use of a pacifier, gentle stroking, and allowing the newborn or infant to hold a comfort item or blanket. Oral sucrose administration, as well as breastfeeding or breast milk, can reduce the pain in newborns.[22][16]

Opiates by and large are the primary agents for pharmacologic pain management in the prehospital system, with morphine and fentanyl being the primary forms of opiates used.[23]  Additional pharmacologic interventions would include NMDA receptor antagonists (ketamine), benzodiazepines (diazepam, lorazepam, and midazolam), nonsteroidal anti-inflammatories (ibuprofen, ketorolac) and other non-opiate pain medications (acetaminophen/paracetamol).

• Non-opiate pain medication is considered one of the first-line treatment options for acute pain for non-healthcare individuals.  The (2) primary classes include aniline analgesics and non-steroid anti-inflammatories.   The primary mechanism of action for both NSAIDs and acetaminophen (which is a non-opiate analgesic) is by the reduction of prostaglandins in the brain by reducing cyclooxygenase (COX inhibitors).   Additional non-opiate analgesic medications include nitroglycerin.
  • Aniline analgesics are a class of medications first produced in 1886 with acetanilide being the first drug of this class with its major metabolite being paracetamol, but its use was stopped because of the cyanosis due to methemoglobinemia.  Phenacetin (synthesized by Bayer in 1887) and paracetamol (synthesized at Johns Hopkins University in 1887) are additional aniline derivatives.  Phenacetin gained faster acceptance over paracetamol because the original thinking was that paracetamol to produced methemoglobinemia, but in the 1940s, research disproved this and determined that phenacetin metabolized to paracetamol. In the 1980s, phenacetin was banned secondary to hematological toxicity, analgesic nephropathy, and abuse due to psychotropic effects.
    • Acetaminophen/Paracetamol (para-acetylaminophenol or NPAP)
      • First created in 1887 and has been one of the most commonly used pain- and fever-reducing medications in the Americas and Europe. It has been listed by the World Health Organization (WHO) as an essential medication and is deemed safe in pregnancy. It has many medical uses, including fever reduction, mild to moderate pain management, and has been combined with opioids to improve analgesic effects. Adverse effects include liver damage (either in acute overdoses or with chronic use) via the toxic intermediate product NAPQI (N-acetyl-p-benzoquinone imine) and recent FDA warning about rare development of Stevens-Johnson syndrome and toxic epidermal necrolysis. Mechanism of action is with COX-2 inhibition and within the hypothalamus to produce antipyresis.
      • Para-acetylaminophenol breaks down into three separate metabolites via different processes that include: (1) glucuronidation, (2) sulfation, and (3) N-hydroxylation by cytochrome P-450.   NAPQI is the toxic metabolite that is produced during the N-hydroxylation process and reacts to sulfhydryl groups of glutathione to produce harmless metabolites.
      • Kinetics / dynamics
        • Pregnancy category: C (crosses placenta)
        • Half-life: 1.25 to 3 hours
        • Onset: 10 to 60 minutes
        • Duration: 4 to 6 hours
      • Dosing
        • Adult
          • PO: 325 to 1000 mg every 4 to 6 hours NMT 4 grams/day
        • Pediatric
          • PO: 10 to 15 mg/kg every 4 to 6 hours
      • Precautions
        • Potential toxic dose 150 mg/kg
        • Can cause allergic reaction/angioedema
        • Renally excreted in the sulfated and glucuronidated metabolite forms
        • 10% metabolizes to NAPQI, which can if it does not undergo glutathione conjugation, accumulate in the hepatocytes resulting in hepatic toxicity.
  • Nonsteroidal anti-inflammatories (NSAIDs) break down into either COX-1 and COX-2 inhibitors with both isozymes having a similar mechanism of action of inhibiting the breakdown of arachidonic acid with downstream reduction of prostaglandins, thromboxane, and prostacyclin.[24] This class of medication, when not contraindicated, can be used separately as being favored over acetaminophen (paracetamol) due to the anti-inflammatory properties or in conjunction with acetaminophen (paracetamol) with synergistic effects.[25]
    •  Ibuprofen
      • Nonselective cyclooxygenase (COX) inhibitor
      • Kinetics/dynamics
        • Pregnancy category: D (B if not used for prolonged periods, or not near term)
        • Half-life: 2 to 4 hours
        • Onset: 30 minutes
        • Duration: 4 to 6 hours
      • Dosing
        • Adult
          • PO: 200 to 400 mg every 4 to 6 hours
        • Pediatric
          • PO: 5 to 10 mg / kg every 4 to 6 hours
      • Precautions
        • Use lowest effective dose for the shortest possible duration to reduce risk of adverse events
        • Risk of serious cardiovascular thrombotic events (MI, stroke)
        • Avoid in patients with recent MI unless the benefit outweighs the risk; monitor for S/S of ischemia
        • Risk of serious GI events including inflammation, perforation, bleeding, and ulceration
      • Contraindications
        • Patients on blood thinners
        • Infants < 6 months of age; not approved by FDA
        • Active gastrointestinal bleeding or peptic ulceration
        • known hypersensitivity reaction to ibuprofen, aspirin or other NSAIDs
    • Ketorolac tromethamine
      • Kinetics/dynamics
        • Pregnancy category: C
        • Half-life: 2.5 hours
        • Onset: 1 to 3 minutes
        • Duration: 5 to 6 hours
      • Dosing
        • Adult
          • IV: 15 to 30 mg
          • IM: 30 to 60 mg
        • Pediatric
          • Safety and efficacy not established
      • Precautions
        • Do not exceed 5-day duration for any combination of routes/forms
        • Can cause serious GI events (bleeding, perforation, ulceration); use lowest effective dose and duration to reduce risk
        • Long-term Tx: risk of renal papillary necrosis, interstitial nephritis, and nephrotic syndrome
        • Risk of renal decompensation; correct volume depletion before initiation and maintain hydration
        • Monitor renal function with renal impairment and those at risk
        • May cause or exacerbate hypertension; monitor during Tx
        • May cause fluid retention/edema, NaCl retention, hyperkalemia, oliguria, edema, serum urea nitrogen and creatinine elevations
  • Nitroglycerin is an organic nitrite that has potent vasodilatory effects. The first described use for nitroglycerin in medicine dates back to 1867 when Lauder Brunton treated patients with angina. Today nitroglycerin is on the World Health Organization's list of essential medications. [26] Nitroglycerin causes smooth muscle dilation by decreasing the cytosolic calcium levels. This process occurs through the release of nitrous oxide that stimulates the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), which acts as a cellular messenger.  cGMP stimulates protein kinase P, which is a second messenger that causes a drop in the cytosolic calcium and, therefore, smooth muscle dilation.
    • Kinetics/dynamics
      • Pregnancy category: C
      • Half-Life: 1 to 4 minutes
      • Onset:
        • Antianginal effects: within 2 minutes
        • Hemodynamic effects: 2 minutes
      • Duration:
        • Antianginal effects: up to 30 minutes
        • Hemodynamic effects: up to 30 minutes
    • Dosing
      • Angina pectoris
        • Sublingual - 0.3 mg q 5 minutes
        • Transdermal - 0.5 to 2 inches every 8 hours
      • Congestive Heart Failure
        • Transdermal - 1.5 inches, increase by 0.5 to 1 inch up to 4 inches
    • Precautions
      • Can cause an increase in ICP and hypotension
      • Discontinue if blurred vision develops
      • Headache; dose-related
      • Do not apply with fingers; do not rub or massage

"Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium" Sir Thomas Sydenham, 1680.[27] Opiate pain medications bind directly to (3) different receptors in the brain to include: mu, delta, and kappa.  The mu receptor is the primary receptor for opiates and was first described in the 1800s after the formulation discovery for morphine, named after the Greek God of Sleep Morpheus.  Opiates work by activating a g-protein secondary message system through the coupling of the opiate with the mu-opioid receptor (MOR) in the central nervous system.[28] Mu receptors are located throughout the body, but specifically in the periaqueductal gray (PAG) found in the midbrain.  One of the functions of the PAG is to control descending pain modulation through the suppression of pain via enkephalin-producing cells. Gamma-aminobutyric acid (GABA), which is the chief inhibitory neurotransmitter, plays an important role in the suppression of pain by preventing the transmission of pain signals along the nerve.[29] Opiate medications will decrease glutamatergic (excitatory) and GABAergic (inhibitory) activity depending upon the location within the brain and spinal cord.  The reduction of glutamatergic synaptic transmission will give the desired properties of analgesia.  The reduction in GABAergic activity specifically within the nucleus accumbens allows for an increase in dopamine and thus gives the "reward" or euphoric effects associated with opiates.

• Morphine is a derivative of opium extracted from the poppy seeds of the opium poppy. Morphine is an agonist with the mu-opioid receptor (MOR), K-opioid receptor (KOR), and delta-opioid receptor (DOR).   Analgesia, sedation, respiratory depression are associated with the (MOR) activation, whereas miosis (pinpoint pupils), spinal analgesia, and psychotomimetic effects are associated with the (KOR) activation.[30][31]
  • Kinetics/dynamics
    • Pregnancy category: C
    • Half-life: 1.5 to 4.5 hours (immediate-release forms)
    • Onset: IV < 5 minutes
    • Duration: up to 7 hours
  • Dosing
    • Adult
      • IV: 2 to 10 mg over 3 to 5 minutes
      • IM: 5 to 20 mg
    • Pediatric:
      • IV / IM: 0.1 - 0.2 mg/kg
  • Adverse effects morphine includes CNS and respiratory depression, bradycardia, QT-interval prolongation, miosis, constipation (ileus), urinary retention, allergic reaction related to histamine release from mast cells, hypogonadism, dependency, and addiction.[31]
• Fentanyl is a mu-selective synthetic opiate first synthesized in the 1960s and medically approved for pain control and medication-assisted intubation. Its potency is approximately 100 times more than morphine.[32]
  • Kinetics/dynamics
    • Pregnancy category: B
    • Half-life: 7.1 hours
    • Onset: Immediately
    • Duration: up to 72 hours
  • Dosing
    • Adult
      • IV / IM: 1 to 2 mcg/kg (usual dose 50 to 100 mcg)
    • Pediatric
      • IV / IM: 1 mcg/kg
  • Adverse effects include respiratory depression, somnolence, asthenia (weakness), constipation, urinary retention. Rapid administration can produce chest wall rigidity.[32]
• Hydromorphone (dihydromorphinone) is a synthetic opiate patented in 1923. It exerts its effects on mu-opioid receptors.  It has a high potency (0.9 to 1.2 mg) equianalgesic when compared to morphine sulfate (10 mg) and is used to treat moderate to severe pain.[33][34]
  • Kinetics/dynamics
    • Pregnancy category: C (D if used near term, according to some authorities)
    • Half-life: 2 to 4 hours
    • Onset: 10 to 15 minutes
    • Duration: 2 to 3 hours (IV)
  • Dosing
    • Adult
      • IV: 0.2 to 1 mg every 2 to 3 hours
      • IM: 1 to 2 mg every 2 to 3 hours
    • Pediatric
      • IV/IM: 0.015 mg / kg slow IV/IM every 4 - 6 hours
  • Adverse effects include risk of respiratory depression, bronchospasm, urinary retention, dizziness, circulatory depression, nausea, itchiness, and constipation

Benzodiazepine (BZD) is a classification of medications that act as positive allosteric modulators at the BZD receptor (gamma-aminobutyric acid (GABA)-A receptor) site which is a ligand-gated chloride-selective ion channel. GABA is the primary inhibitory neurotransmitter in the central nervous system. BZDs classification is in terms of the half-life elimination with a short-acting half-life of 1 to 12 hours, the intermediate-acting half-life of 12 to 40 hours, and long-acting of 40 to 250 hours. Common side effects for all BZDs include lethargy, fatigue, and drowsiness. Impaired motor coordination, blurring of vision, slurring of speech, mood swings, with feelings of euphoria can present in patients with higher dosage consumption.[35] The different formulations of benzodiazepines have different routes of degradation, with the majority of them being first metabolized by hepatic oxidation and then undergo glucuronidation, these being chlordiazepoxide, diazepam, and midazolam. There are (3) that only undergo hepatic glucuronidation, which is lorazepam, oxazepam, and temazepam. Administration of benzodiazepine type medication to elderly patients and those persons with liver disease requires careful consideration because the benzodiazepine oxidation decreases.[36] 

• Diazepam
  • Kinetics/dynamics
    • Pregnancy category: D
    • Half-life: 20 to 70 hours (active metabolite)
    • Onset: 1 to 5 minutes (IV / IM)
    • Duration: 15 to 60 minutes
  • Dosing
    • Adult
      • Alcohol withdrawal
        • IV: 10 mg initially followed by 5 to 10 mg every 1 to 4 hours
      • Muscle relaxant
        • IV/IM: 5 to 10 mg every 3 to 4 hours
      • Seizure disorder / status epilepticus
        • IV/IM: 5 to 10 mg/dose every 10 to 15 minutes
    • Pediatric
      • Muscle relaxant
        • IV/IM: 0.04 to 0.2 mg/kg every 2 to 4 hours
      • Seizure disorder / status epilepticus
        • Neonate (< 28 days)
          • IV: 0.3 to 0.75 mg / kg every 15 to 30 minutes x 2 to 3 doses
        • > 1 month
          • IV: 0.2 to 0.5 mg/kg every 15 to 30 minutes x 2 to 3 doses
  • Precautions
    • Not recommended for MAI / RSI because of the time of onset, but used frequently for long-term sedation following intubation. 
    • It requires propylene glycol as a diluent, and there are reports of propylene glycol toxicity associated with long-term infusions.
    • Undergoes hepatic oxidation and glucuronidation f metabolized
• Lorazepam [37]
  • Kinetics/dynamics
    • Pregnancy category: D
    • Half-life: 8 to 20 hours
    • Onset:
      • IV: 1 to 5 minutes
      • IM: 15 to 30 minutes
    • Duration: 12 to 24 hours
  • Dosing
    • Adult
      • Sedation
        •  IV: 0.02 to 0.06 mg / kg
      • Seizure disorder / status epilepticus
        • IV: 2 to 4 mg
    • Pediatric
      • Sedation
        • IV: 0.025 to 0.05 mg/kg
      • Seizure disorder / status epilepticus
        • IV: 0.05 to 0.1 mg/kg every 10 to 15 minutes
  • Safer to use in patients with impaired liver function than other benzodiazepines because it only requires hepatic glucuronidation into lorazepam-glucuronide.[36]
  • Precautions
    • Not recommended for MAI / RSI because of the time of onset, but used frequently for long-term sedation following intubation. 
    • It requires propylene glycol as a diluent, and there are reports of propylene glycol toxicity associated with long-term infusions.
• Midazolam [38][39][40][39][38]
  • Kinetics/dynamics
    • Pregnancy category: D
    • Half-life: 1.2 to 12.3 hours
    • Onset:
      • IV: 2 to 3 minutes
      • IM 15 minutes
    • Duration: 1 to 4 hours
  • Dosing
    • Adult
      • Medication-assisted intubation / Rapid Sequence Intubation
        • IV: 0.1 to 0.3 mg/kg IV push, with a time to initial effect of roughly 30 to 60 seconds, and a duration of action of 15 to 30 minutes
        Sedation
        • IV: 0.5 to 1 mg
      • Seizure disorder / status epilepticus
        • IV/IM/IN: 2 to 4 mg every 10 to 15 minutes
    •  Pediatric
      • Medication-assisted intubation / Rapid Sequence Intubation
        • IV: 0.1 to 0.3 mg/kg IV push, with a time to initial effect of roughly 30 to 60 seconds, and a duration of action of 15 to 30 minutes
        Sedation
        • IV: 0.05 - 0.1 mg/kg
      • Seizure disorder / status epilepticus [41]
        • IV: 2 to 4 mg every 10 to 15 minutes
        • IM: 0.1 to 0.5 mg/kg
        • IN: 0.1 to 0.2 mg/kg
  • Precautions
    • Not recommended for MAI / RSI because of the time of onset, but used frequently for long-term sedation following intubation. 
    • Undergoes hepatic oxidation and glucuronidation for metabolism

NMDA (N-methyl-D-aspartate) receptor antagonists are a group of medications that can induce a state of dissociation and, therefore, can produce anesthesia characterized by loss of short term memory (amnesia), inability to feel pain (analgesia) and decreased sensitivity to pain (catalepsy).  The primary role is to inhibit the action of glutamate, which is the primary excitatory neurotransmitter of the brain and spinal cord.  These medications have been used to treat acute and chronic pain syndromes. 

• Ketamine 
  • First described in 1966 by Corssen and Domino as a human anesthetic.[42] Ketamine has (3) primary functions to being: hypnotic (sleep-producing), analgesic (pain-relieving), and amnestic (short-term memory loss) effects, which are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Additionally, ketamine causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system, which can cause tachycardia and hypertension.[43][44][45] Ketamine has become widely used as an induction agent during medication-assisted intubation for patients with asthma and COPD because of the bronchodilation properties.
  • Kinectics/dynamics
    • Pregnancy category: C
    • Half-life:
    • Onset:
      • IV: 30 seconds
      • IM: 3 to 4 minutes
    • Duration:
      • IV: 5 to10 minutes
      • IM: 12 to 25 minutes
  • Dosing
    • Adult
      • Medication assisted intubation / Rapid Sequence Intubation
        • IV: 1 to 2 mg/kg
        • IM: 4 mg/kg
      • Sedation
        • IV: 1 to 2 mg/kg
        • IM: 4 mg/kg
    • Pediatric
      • Medication assisted intubation / Rapid Sequence Intubation
        • IV: 1 to 2 mg/kg
        • IM: 4 mg/kg
      • Sedation
        • IV: 1 to 2 mg/kg
        • IM: 4 mg/kg
  • Precautions
    • > 10 % -  hypertension and tachycardia
    • < 1 % - hypersalivation, increased IOP, increased metabolic rate, hypertonia, laryngospasm

(kinectics / dynamics / dosages / precautions obtained from PEPID online)

From the five known most frequent causes for individuals to call for emergency services, three of them are pain-related ("wounds, fractures, minor injuries," "accidents," "chest pain/heart disease").[3] This means that prehospital providers have a potential impact on the pain/suffering of individuals that rely on the services provided. Prehospital providers need to assess patients for pain with appropriate validated tools.  Prehospital providers have pharmacologic and non-pharmacologic modalities at their disposal to render compassionate care to the individuals they are treating. It is crucial to be familiar with the different agents available to include indications, contraindications, adverse risk factors, dosages, and potential reversal agents. Likewise, prehospital providers should be more willing to utilize non-pharmacologic modalities for pain management.