|
 
 |
| REVIEW ARTICLE |
|
| Year : 2020 | Volume
: 18
| Issue : 3 | Page : 222-228 |
|
Pain management in acute trauma
Surendra Kumar Muthyala1, Aparna Lohanathan1, Suma Mary Thampi2, Kanika Singh3
1 Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Paediatric Anaesthesiology, Starship Hospital, Auckland, New Zealand
3 Department of Trauma Anaesthesia, RIMS Trauma Centre, Ranchi, Jharkhand, India
| Date of Submission | 10-Jan-2020 |
| Date of Decision | 20-Jan-2020 |
| Date of Acceptance | 15-Feb-2020 |
| Date of Web Publication | 10-Jul-2020 |
Correspondence Address:
Dr. Suma Mary Thampi
Department of Paediatric Anaesthesiology, Starship Hospital, Auckland
New Zealand
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/cmi.cmi_9_20
Pain is one of the most common complaints among patients presenting to the emergency department (ED), and almost all conscious trauma patients would experience pain as the most troubling symptom. The acute management should include initial appropriate assessment of severity of pain and various measures to relieve acute pain. Multimodal analgesia which includes multiple analgesic medications (opioid and nonopioid), regional anesthesia, and nonpharmacologic interventions (physical and cognitive strategies) is highly efficient for effective and immediate pain relief. Regional anesthesia, which is gaining popularity in the ED as an integral part of acute pain relief due to trauma, includes peripheral nerve blocks and local neuraxial blockade and significantly alleviates pain and improves patient comfort.
Keywords: Pain, pain management, pain relief, regional anesthesia, trauma
How to cite this article:
Muthyala SK, Lohanathan A, Thampi SM, Singh K. Pain management in acute trauma. Curr Med Issues 2020;18:222-8 |
| Introduction | |  |
Trauma is a major cause of morbidity and mortality in both developed and developing countries.[1],[2],[3] Majority of trauma deaths occur in the prehospital period due to insufficient prehospital care where the first 60 min after a trauma has been considered as the “golden hour” of trauma.[4],[5],[6] Pain is perhaps the most common presenting complaint of patients presenting with acute emergencies. The International Society for the Study of Pain Task Force November 2019 defined pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”[7] Majority (75%–80%) of patients presenting with acute trauma complain of pain and almost everybody with trauma would experience pain as the main symptom.[2],[3]
Physiology of pain
Pain is a very important sensory modality identified by specific pain receptors. These receptors are nerve endings, present in most organs and respond to damaging or potentially damaging stimuli. Messages initiated by these noxious stimuli are transmitted by specific, sensory nerves to the spinal cord. The sensitive nerve ending (pain receptors) in the tissue and the sensory nerve that carries impulses together form a unit called the primary afferent nociceptor. The second-order neurons in the spinal cord then relay the message through well-defined pathways to higher centers. These include reticular formation in the brain stem, thalamus, somatosensory cortex, and limbic system. The thalamus and cortex are the primary areas involved in processing pain perception.[8],[9]
Acute management of pain due to trauma
Patients with trauma are often in a lot of distress due to the intensity of the pain, compounded by their several other problems. The acute management in the emergency department (ED) should include initial appropriate assessment of the severity of pain and various measures to relieve acute pain. The use of multimodal analgesia (MMA) is recommended for acute pain relief. MMA, also known as balanced analgesia, refers to the use of multiple medications for analgesia and nonpharmacologic interventions for effective and immediate pain relief.[10],[11]
These include:
- Pharmacological intervention (opioid and nonopioid)
- Physical strategies
- Regional analgesia
- Psychological intervention.
Assessment of the severity of pain
It is important to assess the severity of pain as soon as the patient is brought to the ED. The universal pain assessment tool is a standard and validated tool for assessing the severity of pain in patients with a normal sensorium [Figure 1]. This combines pictures (Wong-Baker faces) and numbers for pain rating called “Numerical Rating Scale.” Zero indicates the absence of pain and 10 represents very severe pain. The assessment is carried out by asking the patient to point out the picture that best describes the intensity of the pain or the numerical value of the severity of the pain he/she is currently experiencing.[12]
Timeline to assess pain:
- At the time of initial presentation or at an acute change in the character of pain
- Reassess every 30 min after administering intravenous analgesic till target score is achieved
- After that, reassess every 1 h for 4 h.
| Pharmacological Interventions | | |
Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used drugs for acute pain management in trauma.
Morphine
Morphine is a very potent opioid analgesic that can be administered orally, intravenously, intramuscularly, subcutaneously, or by the epidural route. Its active metabolite is morphine-6-glucuronide, which has an analgesic effect and is the first-choice opioid in the treatment of severe nociceptive pain.[13],[14] The onset of action is 5 min, 15 min, and 20 min by intravenous, intramuscular, and oral route, respectively. It is strongly recommended that all opioid administration is accompanied by an antiemetic like ondansetron. The recommended dosing is 0.1 mg/kg bolus, followed by 0.05 mg/kg every 30 min. It should be remembered that peak analgesic effects may not be seen up to 20 min later.[15] It is to be avoided in traumatic brain injury, biliary colic, history of allergy to morphine, or if there is a chance of respiratory depression. Dose reduction is required in patients with adrenocortical insufficiency, impaired liver or renal function, and shock and in aged patients. Patients should be observed for a decrease in respiratory rate, hypotension, vomiting, or sedation.
Fentanyl
Fentanyl, a derivate of phenylpiperidine, is another potent opioid analgesic. In comparison to morphine, it has almost immediate action, which makes it ideal for patients in severe pain. It also has less pro-emetic effects. Although transdermal patches are available for the convenience of use, fentanyl patches have long absorption life of 16–20 h after removal and hence may cause fatal respiratory depression even after the pain has subsided.[16],[17] Even though the risk of fentanyl induced hypotension is quite low, it is best to be cautious in cardiac/atherosclerotic patients. The recommended dosing is 1–2 μg/kg bolus, followed by 1 μg/kg every 30 min. Fentanyl is also best avoided in traumatic brain injury, biliary colic, and if the history of allergy to fentanyl is present. As with morphine, patients should be watched for sedation, decrease in respiratory rate, and vomiting.
Tramadol
It is an opioid analgesic used for a variety of moderate to moderately severe painful conditions and is quite effective for patients with mixed nociceptive and neuropathic pain. It binds to μ-receptors and weakly inhibits the reuptake of norepinephrine and serotonin producing a central opioid analgesic effect. Its onset is 10–15 min and duration of action is 4–6 h.[18],[19] Although considered to be a relatively safe analgesic, central nervous system (CNS) side effects are common after administration and included headache, drowsiness, and respiratory depression. Respiratory depression is not commonly seen with therapeutic doses; however, it should be avoided in those with diminished respiratory functions.[20] Contraindications for its use include hypersensitivity, severe respiratory depression, acute or severe bronchial asthma, and gastrointestinal (GI) obstruction.
Paracetamol
It is the most commonly used over-the-counter analgesic and is an effective analgesic for mild-to-moderate pain.[19] It is available as a sole agent or in combination with NSAIDs and opioids. Normal adult dose is 325–650 mg every 4–6 h as needed or 1 g every 6 h as needed with a maximum dose of 4 g/day. Absorption from the GI tract is rapid, and peak serum concentration occurs in 30 min to 2 h.[21],[22] It has no significant side effects. It can be used in all patients without renal or hepatic injury. 15–20 mg/kg bolus in 100 ml NS dose may be repeated every 6 h (without hepatic injury). It is contraindicated in patients with severe hepatic dysfunction.
Codeine
It is an opioid analgesic which is not widely used due to its unreliability since its analgesic effect is dependent on the conversion of codeine into its active metabolites, codeine-6-glucuronide, and morphine. It has decreased efficacy in patients deficient in the enzyme required for the conversion and causes opioid toxicity in hyper metabolizers of codeine.[22]
Nonsteroidal anti-inflammatory drugs
NSAIDs are a class of drugs with both analgesic and anti-inflammatory properties and have a significant opioid dose-sparing effect. These agents do not cause sedation or respiratory depression and there is no risk of dependence or addiction. As analgesics, they act by inhibiting the cyclooxygenase2 enzyme in the spinal cord, thereby decreasing the excitability of dorsal horn neurons that produce hyperalgesia and allodynia.[23],[24] There is a wide range of NSAIDs with different potencies and side effects. Diclofenac is one of the most commonly used NSAIDs. It has the highest potency for pain relief but causes significant GI upset and increased risk of cardiovascular adverse effects even at low doses. Naproxen, on the other hand, has an equally good efficacy but relatively lower GI side effects and is risk neutral with regard to cardiovascular adverse events. Ibuprofen has the least GI side effects but its potency is comparatively lower; hence, it is used for mild-to-moderate pain relief for a prolonged period of time. The most common side effects related to NSAIDs are GI upset, platelet dysfunction, renal dysfunction, and increased risk of cardiac death in patients with ischemic heart disease. Contraindications for their use include active GI ulcers or active GI bleeding, cerebrovascular bleeding or other bleeding disorders, severe renal impairment (CrCl <30 mL/min), and severe uncontrolled heart failure.
| Physical Strategies | | |
Simple physical measures such as immobilization and splinting of the involved extremity offer significant relief of acute pain. Additional measures such as ice pack application for mild-to-moderate sprains and limb elevation when appropriate also help in alleviating pain due to trauma.
| Regional Analgesia | | |
Regional anesthesia is an integral part of acute pain relief due to trauma. Peripheral nerve blocks and local neuraxial blockade significantly alleviate pain and improve patient comfort. In addition, they reduce the requirement for systemic opioid analgesia and thereby minimize the adverse effects associated with opioid use.[25],[26]
Nerve blocks
Nerve blocks should be administered to all patients requiring emergency procedures such as debridement, dressing, fracture reduction, and wound wash with or without procedural sedation. Digital nerve block, wrist block, and ankle block are the most commonly administered blocks and do not necessarily require ultrasound guidance as they are relatively safe and simple to perform.[26] The choice of the local anesthetics (LAs) depends on the desired duration of the block. 2% lignocaine is used for a shorter duration of the blockade, while 0.5% bupivacaine is used for a longer blockade. The pharmacological characteristics of commonly used LAs are shown in [Table 1].
| Digital Nerve Block (Finger Web Space Block) | | |
In this procedure, a LA solution is injected into the base of a finger or toe (web space) to provide regional anesthesia. This can be done for conditions such as finger or toe lacerations, nail bed injuries, paronychia drainage, and nail avulsion.
Contraindications
- Infection at the site of block
- Allergy to the LA
- Compromised circulation in the digits.
Technique
- Prepare the web space concerned with chlorhexidine solution
- Place the hand flat with the palmar side down on a sterile drape [Figure 2]
- Aspirate before injecting the drug to rule out the intravascular injection
- Inject 2 ml 2% lignocaine/0.5% bupivacaine into the subcutaneous tissue of web space at the base of the finger just distal to the metacarpophalangeal joint using a 26 G hypodermic needle
- Withdraw the needle completely and repeat the procedure on the web space of the opposite side of the finger.
It is important to remember that it takes at least 10 min for the LA to take complete effect, and hence, it is important to wait before starting the surgical procedure. It is imperative to avoid using adrenaline with the LA in a digital block to avoid the risk of ischemic injury to the digit. A relatively high pressure required for injection could indicate needle placement directly in the nerve and should be avoided.
| Wrist Block | | |
A wrist block is a procedure in which the terminal branches of the ulnar nerve, median nerve, and radial nerve are blocked separately by administering a LA. It is indicated for surgeries of the hand, fingers, and carpal tunnel.
Contraindications
Contraindications include infection at the site of block and allergy to the drug.
Median nerve block
The median nerve is located in the flexor retinaculum between the tendons of flexor palmaris longus and flexor carpi radialis. The flexor palmaris can be identified by asking the patient to oppose the thumb and the little finger. The technique of administering the block is shown in [Figure 3].
Technique
- Insert a 26 G needle between tendons of flexor palmaris longus and flexor carpi radialis until it hits a bone
- Inject about 3–5 ml of LA after ruling out intravascular injection by negative aspiration.
Ulnar nerve block
The ulnar nerve runs between the ulnar artery and the flexor carpi ulnaris tendon (the most medial tendon palpable). The technique of administering the block is shown in [Figure 3].
Technique
- Insert a 26 G needle under the flexor carpi ulnaris tendon and advance about 5–10 mm laterally
- After negative aspiration, inject about 3 ml of LA.
Radial nerve block
The radial nerve emerges between the brachioradialis tendon and the radius just proximal to the styloid process and becomes superficial to supply the dorsum of the hand. As the radial nerve has a less predictable anatomic location and divides into multiple smaller cutaneous branches, a more extensive infiltration is required. The technique of administering the block is shown in [Figure 4].
Technique
- Insert a 26 G needle just proximal to the styloid process of the radius in the anatomical snuffbox and aim medially
- After negative aspiration, inject about 3 ml of 2% lignocaine
- After that, direct the needle laterally and inject an additional 3 ml of LA subcutaneously in fan-shaped manner.
| Ankle Block | | |
The ankle block is used for surgery on the foot and toes and is a purely sensory block. It consists of separate blocks of five nerves [Figure 5]:
- Four branches of the sciatic nerve
- Superficial peroneal (fibular) nerve
- Deep peroneal (fibular) nerve
- Tibial nerve
- Sural nerve.
- One cutaneous branch of the femoral nerve
The anatomy of these peripheral nerves around the ankle is shown in [Figure 6].
To administer any of these ankle blocks, the patient should be positioned supine, with the foot elevated and supported on blankets or pillows, and the ankle rotated as necessary for needle placement. Contraindications are similar to other superficial blocks and include infection at the site of block and allergy to the drug.
Deep peroneal nerve block
Technique
- Palpate the dorsalis pedis artery between the tendons of flexor hallucis longus and extensor digitorum longus tendons. These tendons can be identified by having the patient flex the great toe. The nerve lies just lateral to the artery
- At the mid-tarsal portion of the foot, insert the needle just lateral to the artery and advance until the bone is encountered
- Inject 2–3 ml of LA in the deep plane as the needle is slowly withdrawn.
Superficial peroneal nerve block
Technique
- The superficial peroneal nerve innervates the dorsum of the foot and is blocked by subcutaneous infiltration of LA
- Insert the needle at the injection site for deep peroneal nerve block
- Inject about of 5–10 ml of LA subcutaneously over the dorsum of the foot medially and then laterally from the site of needle insertion to the level of the malleoli.
Posterior tibial nerve block
Technique
- The distal tibial nerve provides sensation to the calcaneus and plantar surface (sole) of the foot and is blocked at the level of the medial malleolus
- Palpate the posterior tibial artery behind the medial malleolus
- Insert the needle posterior to the artery and advance until the bone while aiming toward the malleolus at a 45° angle
- After negative aspiration, inject 2–3 ml of LA
- To increase the success rate of the block, inject an additional 1–2 ml of LA using a fan technique, medially and laterally.
Sural nerve block
Technique
- The sural nerve innervates the lateral ankle and foot, as well as the fifth toe. It runs within the subcutaneous tissues behind the lateral malleolus
- Insert the needle subcutaneously just behind the lateral malleolus
- Inject 2–3 ml of LA behind the lateral malleolus as a subcutaneous wheal.
Saphenous nerve block
Technique
- The saphenous nerve innervates the medial aspect of the ankle and foot. It is blocked at the ankle using anatomic landmarks
- Insert the needle posterior and superior to the medial malleolus and direct it posteriorly toward the Achilles tendon
- After negative aspiration, inject 2–3 ml of LA as a subcutaneous wheal.
| Nerve Blocks for Rib Fractures | | |
Pain management in patients with rib fractures can be quite challenging. In patients with one or two rib fractures, systemic opioids and analgesics may suffice. Patients with multiple rib fractures may require an intercostal nerve block, thoracic epidural, or thoracic paravertebral blocks. Ultrasound-guided myofascial plane blocks that include erector spinae plane block and the serratus anterior plane block are quite promising modalities for pain relief in patients with multiple rib fractures. The myofascial plane blocks are less invasive and can be administered early on in the ED itself.
| Local Anesthetic Systemic Toxicity | | |
Although generally safe, LA agents can have systemic toxicity if injected directly into the vasculature inadvertently. Data suggest that 1:500 peripheral nerve blocks result in systemic toxicity. Local anesthetic systemic toxicity (LAST) affects the CNS or the cardiovascular system (CVS).[27],[28],[29] Its manifestations typically appear 1–5 min after the LA injection. However, the onset of symptoms may range from 30 s to 60 min.[29]
- CNS manifestations: The initial symptoms of systemic toxicity are of CNS excitement (circumoral and/or tongue numbness, lightheadedness, dizziness, metallic taste, muscle twitching, and convulsions) followed by CNS depression (unconsciousness, respiratory depression, coma, and respiratory arrest)
- CVS manifestations: Chest pain, breathlessness, palpitations, sweating, hypotension, and syncope
- Hematologic manifestations: Methemoglobinemia (benzocaine, lidocaine, and prilocaine)
- Allergic manifestations: Rash, urticaria, and anaphylaxis (very rare).
We highly recommend to follow the Third American Society of Regional Anesthesia and
Pain Medicine Practice Advisory on LAST.[30] Extremes of age (<16 years and > 60 years), low muscle mass, and female sex are risk factors for LAST.[30]
Recommendations for the treatment of local anesthetic systemic toxicity
It is important to establish the diagnosis of LAST to initiate emergency management which includes the following:
Airway management
Keep the airway patent through airway maneuvers to prevent hypoxia, hypercapnia, and acidosis which are known potentiating factors for LAST.
Seizure suppression
Benzodiazepines or barbiturates can be used for control of seizures. Although propofol is effective for seizure control, large doses may depress myocardial function and hence should be avoided if there are features of cardiotoxicity due to LAST.
Management of cardiac dysrhythmias
An electrocardiogram will help in identifying prolonged intervals (PR, QRS, and QT) potentiating reentrant tachycardias with aberrant conduction which may herald CVS toxicity. Advanced cardiac life support guidelines should be followed for the management of arrhythmias in conjunction with lipid therapy.[31] However, the differences from other cardiac arrest scenarios should be kept in mind, in that vasopressin, calcium channel blockers, and other LAs should be avoided.
Lipid emulsion therapy
Cardiac resuscitation may be difficult and prolonged because some LAs are highly lipid soluble and take a long time for redistribution. Intravenous lipid emulsion is an established and effective treatment option for LAST.[32],[33] It is performed with an IV infusion of a 20% solution of lipid emulsion. This infusion creates an expanded lipid phase with the resulting equilibrium driving toxic drug from the tissues to the aqueous plasma phase and then to the lipid phase, a phenomenon described as the “lipid sink.”[34],[35] The composition of intralipid emulsion includes 20% soybean oil, 1.2% egg yolk phospholipids,2.25% glycerin, water, and sodium hydroxide.[33] Although it contains egg and soy, cross allergy to food is not a major concern, and hence, it need not be avoided in patients with allergies to any of these food substances.[36] It may be administered as a bolus or as an infusion. The dose is as follows:
- Bolus dose of 20% lipid emulsion
- Body weight >70 kg (ideal body weight): 100 mL over 2–3 min
- Body weight >70 kg (ideal body weight): 1.5 mL/kg over 2–3 min.
- Infusion dose of 20% lipid emulsion
- Body weight >70 kg (ideal body weight): 200–250 mL over 15–20 min
- Body weight >70 kg (ideal body weight): 0.25 mL/kg/min.
- If hemodynamic stability is not attained, consider a second bolus or increasing the infusion rate to 0.5 mL/kg/min
- Continue the infusion at a rate of 0.25 ml/kg/min for at least 10 min after hemodynamic stability is attained
- The maximum recommended initial dosing is approximately 12 mL/kg of lipid emulsion.
Patients with a significant cardiovascular toxicity should be monitored for at least 4–6 h. If the patient has only CNS symptoms that resolve quickly, they should be monitored for at least 2 h.
| Psychological Interventions | | |
A significant proportion of trauma victims have substantial symptoms of anxiety. In the ED, trauma patients are managed with both medical and surgical interventions for their apparent injuries. However, it is essential to keep in mind the psychological trauma patients suffer secondary to pain, the unexpected nature of events, and the procedures and interventions performed to resuscitate the patient. Both the patients and their families must be provided with psychological support.[37] Medical social workers must be made available in both ED and intensive care units to talk to all patients and their family who sustained trauma, provide them supportive counseling, grief counseling, and help expand their social support. In patients with prolonged hospitalization, early recognition and timely intervention of posttraumatic stress disorder, acute stress disorder, or other psychiatric disorders are of paramount importance in the patient's recovery. Patient's mental health should also be evaluated on a daily basis, and in case, the patient exhibits any symptoms of intense fear or helplessness, anxiety, depression, sleep deprivation, fatigue, headaches, GI, or rheumatic symptoms, immediate psychiatric therapy should be given.[38],[39] Adequate pain relief, preprocedural sedation, reassurance, and early psychotherapy can help avoid these complications.
| Conclusion | | |
Pain due to trauma can be extremely severe and distressing to patients. The use of MMA with multiple analgesic medications (opioid and nonopioid), regional anesthesia, and nonpharmacologic interventions (physical and cognitive strategies) is strongly recommended for efficient and prompt pain relief for acute pain relief in the acute setting.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Hofman K, Primack A, Keusch G, Hrynkow S. Addressing the growing burden of trauma and injury in low-and middle-income countries. Am J Public Health 2005;95:13-7.  |
| 2. | Clement N, Regina DL, Abhilash KP. A retrospective study on the profile and outcome of polytrauma in the emergency department. Curr Med 2018;16:56-9. |
| 3. | Abhilash KP, Chakraborthy N, Pandian GR, Dhanawade VS, Bhanu TK, Priya K. Profile of trauma patients in the emergency department of a tertiary care hospital in South India. J Family Med Prim Care 2016;5:558-63. [ PUBMED] [Full text] |
| 4. | Lerner EB, Moscati RM. The golden hour: Scientific fact or medical “urban legend”? Acad Emerg Med 2001;8:758-60. |
| 5. | McCoy CE, Menchine M, Sampson S, Anderson C, Kahn C. Emergency medical services out-of-hospital scene and transport times and their association with mortality in trauma patients presenting to an urban Level I trauma center. Ann Emerg Med 2013;61:167-74. |
| 6. | Malchow RJ, Black IH. The evolution of pain management in the critically ill trauma patient: Emerging concepts from the global war on terrorism. Crit Care Med 2008;36:S346-57. |
| 7. | Kennedy R, Abd-Elsayed A. The international association for the study of pain (IASP) classification of chronic pain syndromes. In: Abd-Elsayed A, editor. Pain. Springer, Cham; 2019. |
| 8. | Bourne S, Machado AG, Nagel SJ. Basic anatomy and physiology of pain pathways. Neurosurg Clin N Am 2014;25:629-38. |
| 9. | Woolf CJ. Somatic pain-pathogenesis and prevention. Br J Anaesth 1995;75:169-76. |
| 10. | Whipple JK, Lewis KS, Quebbeman EJ, Wolff M, Gottlieb MS, Medicus-Bringa M, et al. Analysis of pain management in critically ill patients. Pharmacotherapy 1995;15:592-9. |
| 11. | Cohen SP, Christo PJ, Moroz L. Pain management in trauma patients. Am J Phys Med Rehabil 2004;83:142-61. |
| 12. | Boonstra AM, Stewart RE, Köke AJ, Oosterwijk RF, Swaan JL, Schreurs KM, et al. Cut-off points for mild, moderate, and severe pain on the numeric rating scale for pain in patients with chronic musculoskeletal pain: Variability and influence of sex and catastrophizing. Front Psychol 2016;7:1466. |
| 13. | McDonald J, Lambert DG. Opioid receptors. Contin Educ Anaesth Crit Care Pain 2005;5:22-5. |
| 14. | Patanwala AE, Duby J, Waters D, Erstad BL. Opioid conversions in acute care. Ann Pharmacother 2007;41:255-66. |
| 15. | Patanwala AE, Keim SM, Erstad BL. Intravenous opioids for severe acute pain in the emergency department. Ann Pharmacother 2010;44:1800-9. |
| 16. | Grissinger M. Inappropriate prescribing of fentanyl patches is still causing alarming safety problems.PT 2010;35:653-4. |
| 17. | Weaver JM. Multiple risks for patients using the transdermal fentanyl patch. Anesth Prog 2014;61:1-2. |
| 18. | Bamigbade TA, Langford RM. Tramadol hydrochloride: An overview of current use. Hosp Med 1998;59:373-6. |
| 19. | Raffa RB, Nayak RK, Minn FL. The mechanism(s) of action and pharmacokinetics of tramadol hydrochloride. Rev Contemp Pharmacother 1995;6:485-97. |
| 20. | Cossman M, Kohnen C. General tolerability and adverse event profile of tramadol hydrochloride. Rev Contemp Pharmacother 1995;6:513-31. |
| 21. | Jefferies S, Saxena M, Young P. Paracetamol in critical illness: A review. Crit Care Resusc 2012;14:74-80. |
| 22. | Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht DE, Homel P, et al. Pain in the emergency department: Results of the pain and emergency medicine initiative (PEMI) multicenter study. J Pain 2007;8:460-6. |
| 23. | Optimizing the treatment of acute pain in the emergency department. Ann Emerg Med 2017;70:446-8. |
| 24. | Friday JH, Kanegaye JT, McCaslin I, Zheng A, Harley JR. Ibuprofen provides analgesia equivalent to acetaminophen-codeine in the treatment of acute pain in children with extremity injuries: A randomized clinical trial. Acad Emerg Med 2009;16:711-6. |
| 25. | Dahl JB, Nielsen RV, Wetterslev J, Nikolajsen L, Hamunen K, Kontinen VK, et al. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: A topical review. Acta Anaesthesiol Scand 2014;58:1165-81. |
| 26. | Choi JJ, Lin E, Gadsden J. Regional anesthesia for trauma outside the operating theatre. Curr Opin Anaesthesiol 2013;26:495-500. |
| 27. | Hughes S, Birt D. Continuous peripheral nerve blockade on OP HERRICK 9. J R Army Med Corps 2009;155:57-8. |
| 28. | Dillane D, Finucane BT. Local anesthetic systemic toxicity. Can J Anaesth 2010;57:368-80. |
| 29. | Butterworth JF 4 th. Models and mechanisms of local anesthetic cardiac toxicity: A review. Reg Anesth Pain Med 2010;35:167-76. |
| 30. | Neal JM, Woodward CM, Harrison TK. The American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2017 Version. Reg Anesth Pain Med 2018;43:150-3. |
| 31. | Groban L, Dolinski SY. Differences in cardiac toxicity among ropivacaine, levobupivacaine, bupivacaine, and lidocaine. Tech Reg Anesth Pain Manag 2001;5:48-55. |
| 32. | Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK. Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth 1997;9:668-70. |
| 33. | Fettiplace MR, Ripper R, Lis K, Lin B, Lang J, Zider B, et al. Rapid cardiotonic effects of lipid emulsion infusion. Crit Care Med 2013;41:e156-62. |
| 34. | Harvey M, Cave G. Lipid emulsion in local anesthetic toxicity. Curr Opin Anaesthesiol 2017;30:632-8. |
| 35. | Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: Proof of clinical efficacy. Anesthesiology 2006;105:7-8. |
| 36. | Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med 2008;51:412-5, 415.e1. |
| 37. | Kelso JM. Potential food allergens in medications. J Allergy Clin Immunol 2014;133:1509-18. |
| 38. | Mollica RF, Cardozo BL, Osofsky HJ, Raphael B, Ager A, Salama P. Mental health in complex emergencies. Lancet 2004;364:2058-67. |
| 39. | van Ommeren M, Saxena S, Saraceno B. Mental and social health during and after acute emergencies: Emerging consensus? Bull World Health Organ 2005;83:71-5. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1]
|
Search Pubmed for