1. Standards
   Class I data regarding management of pain in the prehospital setting is insufficient to support a standard of treatment.
2. Guidelines
   Evidence regarding management of pain in the prehospital setting does not exist to support guidelines on this topic.
3. Options
   1. There are valid reasons to sedate TBI patients (i.e. to reduce the risk of further harm to self or others and to facilitate evaluation or evacuation) and analgesic medications are a standard part of most sedative regimens. In this case, analgesic medications should be administered in small incremental doses and with appropriate physiologic monitoring of blood pressure, oxygenation (PaO2 or SaO₂), and ventilation (pCO2 or EtCO₂).
   2. There is no scientific data or physiologic evidence to support a hypothesis that pain relief improves outcomes in TBI patients, but there is some evidence to support the possibility that the most commonly available analgesic medications (including opiates and Ketamine) increase ICP and may thereby be harmful. Therefore, withholding analgesics from TBI patients who cannot self-score pain (Glasgow Coma Scale score [GCS] < 13; see Guidelines on Assessment: Glasgow Coma Scale Score) for short periods in the prehospital phase, where monitoring is unavailable, is a reasonable option.

Promoting patient comfort and reducing or eliminating pain, while at the same time ensuring patient safety, are responsibilities of all clinicians, including prehospital providers. Prospective randomized controlled studies on the prehospital use of analgesics in TBI patients have not been published. In addition, there is no scientific physiologic evidence to defend or refute the hypothesis that pain management is necessary in the prehospital setting—that relieving pain improves outcomes in TBI patients or that withholding analgesics causes harm. There is, however, evidence to show that all the commonly used analgesics (including opiates and Ketamine) can increase intracranial pressure (ICP) and should therefore be administered in small incremental doses in a monitored setting. Vital signs, such as blood pressure and respiratory rate, which indirectly correlate with ICP and brain tissue oxygenation, are inadequate for monitoring the effects of interventions on brain tissue. Until technology capable of measuring the effects of analgesics on brain tissue is available, the benefit to risk ratio of pain control will remain speculative. However, the use of analgesia and sedation can ease immediate suffering of all TBI patients.

Much of the literature on TBI and pain management is related to the negative effects of chronic pain on all aspects life, but most specifically on the significant hindrance it poses to physical and psychosocial rehabilitation. The pain-fear cycle is a learned behavior that can and should be controlled in order to optimize return to full potential function. In this regard, if a TBI patient is capable of learning to fear pain in the prehospital setting, then early intervention may be desirable.

An MEDLINE search of the literature from 1996 to April 2005 was conducted using the terms "pain" or "analgesics" or "opioid" (yield 35872 articles), "prehospital" or "EMS" (yield 3698 articles), and "brain injuries" or " head (craniocerebral) trauma" (yield 12089 articles). Combined searches including "pain and prehospital" yielded 57 articles and "pain and brain injury" yielded 150 articles. The combination of "brain injury" and "pain" and "prehospital" yielded no articles.

Pain receptors are stimulated by chemicals including bradykinins, serotonin, histamine, potassium ions, acids, some prostaglandins, acetylcholine, and the proteolytic enzymes that are released with tissue damage,1 signaling that some remedial action should be done at once to stop the on-going damage.2 The treatment of pain by itself does not address on-going tissue damage, but is meant to mask the effects of tissue damage. There is no physiologic evidence to support a necessity for pain control.

Objective pain measurements in widely scattered populations of people demonstrate that there is little difference in their recognition of pain thresholds; however, different people do react very differently to perceptions of pain. The perception of pain causes motor reactions such as withdrawal reflexes and psychic disturbances such as agitation and delirium and it is these effects that may be important to treat.2

Ventilated and sedated TBI patients in the ICU showed large transient increases in VO2, energy expenditure, and mean arterial blood pressure in the first 12 hours following cessation of sedation. Although these changes are described as undesirable in head-injured patients, they were not predictive of early neurologic outcome.3

Opiates have analgesic and sedative effects and decrease sympathetic discharge and thus exert a mild negative inotropic and chronotropic effect. They also tend to decrease right ventricular filling due to splanchnic vasodilatation, ultimately resulting in decreased left ventricular enddiastolic pressure. Opiates also exert a direct depressive effect on the medullary respiration center with respiratory rate affected in the early stages before depression of tidal volume as well.1,4 Opioid-induced hypotension is therefore a combination of direct vasodilatation, vagally mediated bradycardia, and histamine release.5

Morphine and fentanyl are the two most commonly used opioids for the analgesia of critically ill patients, including TBI patients, yet the cerebrovascular effects of such drugs remain controversial. In patients with intact autoregulation, reduced MAP would be expected to result in vasodilatation, increased cerebral blood volume, and thus increased ICP; however, studies show that autoregulation may be preserved, impaired, or abolished in TBI patients. Arteriojugular venous oxygen content difference as an estimate of cerebral blood flow can be used to clarify the role of autoregulation and opioid effect on ICP.

Studies consistently show that fentanyl, alfentanil, and sufentanil cause vasodilatation due to a chemical sympathectomy that decreases MAP, which in turn, leads to increases in ICP in neurosurgical patients due to autoregulated vasodilatation to maintain cerebral blood flow in the face of decreased systemic pressure. The findings were consistent in elevated ICP due to head trauma, neoplasia, or hemorrhage.6-10

Data regarding physiologic effects of analgesics on injured brain tissue are yet to be published, and as such, these data have not been analyzed for applicability to this discussion.

While the effects of narcotics in critically ill patients on blood pressure and ICP are well known and predictable, morphine and fentanyl have become drugs of choice in the ICU and in the OR for agitated brain-injured patients with a protected airway because they not only treat pain but have antitussive effects, suppress respiratory drive, and can therefore facilitate compliance with mechanical ventilation, and are reversible with naloxone.

Although there are no randomized trials of individualized therapeutic parameters (MAP and CPP) to allow absolute recommendations on minimally safe standards, most practitioners agree that narcotics are safe in head-injured patients if MAP and CPP can be maintained.11 When changes in MAP are minimized, the effects on ICP can be ameliorated.12-14

Although the need for adequate sedation and analgesia in trauma patients is generally accepted,2,5 there is no consensus regarding which drugs or what specific protocol should be used.15

From the patient point of view, pharmacologic control of pain and anxiety are critical to improving outcome, but many of the opioids may cause nausea, vomiting, vagal or anaphylactic reactions, and have significant detrimental hemodynamic and respiratory side-effects in situations where standard monitoring equipment is limited or not available.16

A number of studies have shown that emergency physicians may not be giving adequate analgesia to patients admitted to the ED or to patients managed by prehospital providers based on fear of adverse opioid side-effects, a belief that pain is needed for making a diagnosis, or priority given to life-threatening disease. A quality control program is necessary in order to measure and positively impact pain management in these settings.17

In a review of the medical, including EMS, literature, Borland et al.18 found a short list of options for safe and effective analgesia for prehospital providers that included nitrous oxide/oxygen mixtures, intravenous/intramuscular nalbuphine, intravenous tramadol, and intravenous pure opiate angonists. There were no prospective or randomized studies.

Tramadol has only weak opioid angonist properties and enhances monaminergic spinal inhibition of pain. When given IV, it is one-tenth as potent as morphine on a weight basis, with onset of action within minutes and duration of effect of 3-6 hours. In comparison with equianalgesic doses of opioids, Tramadol rarely causes respiratory depression and cardiovascular side effects are minor as are episodes of dizziness, nausea, sedation, dry mouth, and sweating. Tramadol is an acceptable alternative to morphine in the prehospital trauma setting.19

There may be valid reasons for wanting to control pain in the prehospital setting if it contributes to anxiety or to harmful activity but there is simply no evidence to indicate whether this is helpful or harmful in this setting. The Hippocratic Rule to "First Do No Harm" should therefore guide commonplace practice. Cautious discriminate use with as much physiologic monitoring as possible is advised.

Pain management for TBI patients in the prehospital setting should be guided by the following principles.

1. In the case of a minor closed head injury (GCS 13-15), a subjective assessment scale should be used before administering any analgesic and again before each additional dose. The goal should be to reduce pain to a level so that the patient remains comfortable but is not obtunded by the medication.
2. In addition to effective pain relief, the ideal analgesic must not alter vital signs, hide complications, or cause delay in therapeutic decision-making.
3. Analgesics should always be administered in small incremental doses.
4. Monitoring should not be limited to intermittent manual observation; the paramedic must be able to use, interpret, and act upon the data derived from patient assessment and monitoring technology to help ensure a positive outcome for the patient.
5. Hypotension (SBP < 90 mm Hg) must be avoided or corrected immediately by administering IV fluids. SBP should be monitored as frequently as possible or continuously. (See Guidelines on Treatment: Fluid Resuscitation.)
6. Oxygen saturation should be monitored as frequently as possible or continuously. Hypoxemia (apnea, cyanosis, or arterial hemoglobin oxygenation saturation [SaO₂] < 90%) must be avoided, if possible, or corrected immediately by administering supplemental oxygen. (See Guidelines on Treatment: Airway, Ventilation, and Oxygenation.)
7. EtCO₂ should be monitored as frequently as possible or continuously. Hypocapnea with hypercarbia (respiratory depression with rise in EtCO₂) causes cerebral vasodilatation and subsequent increased intracranial pressure that must be avoided, if possible, or corrected immediately by administering small incremental doses of Narcan or by assisting ventilation with a bag-valve-mask device or by intubating and placing the patient on a ventilator. (See Guidelines on Treatment: Airway, Ventilation, and Oxygenation).

1. How can the direct or even indirect effects of interventions, including pain control, be monitored in brain-injured tissue, particularly in the prehospital setting?
2. Do TBI patients remember prehospital pain and does this memory hinder ultimate rehabilitation?
3. Are analgesics that do not increase ICP, reduce blood pressure, or depress respiratory drive effective in the prehospital setting?