Old Remedies for Difficult New Conditions

If you’re in EMS long enough, you’ll encounter new conditions that may not be adequately addressed in your textbooks or protocols. Several new problems are now being seen with increasing frequency in both emergency departments and the prehospital setting. These include chronic pain syndrome (CPS), cyclical vomiting syndrome (CVS) and diabetic gastroparesis. These conditions are somewhat enigmatic and notoriously difficult to treat. However, you may already have medications in your formulary that can provide benefit to these difficult groups of patients.

Chronic Pain Syndrome

Chronic pain syndrome (CPS) is a condition being encountered with increasing frequency. Although poorly defined, it is generally considered to be ongoing pain that lasts longer than 3–6 months. Another definition of CPS is pain that persists longer than its reasonably expected healing time. Chronic pain syndrome is generally considered a psychologic-physiologic condition, and its treatment is usually multidisciplinary in nature. 

Most chronic pain patients take multiple medications. Some are on long-term opiates such as morphine, methadone and oxycodone. It has been estimated that approximately 35% of Americans have some degree of chronic pain, with a significant number being disabled due to it. It is more common in women than men and is generally managed using an approach that includes pharmacology, psychotherapy, complementary medicine techniques and other strategies. 

CPS is difficult to treat in the prehospital and emergency department settings. Often patients with CPS are on opiate pain medications that are stronger than those available for paramedics to administer. However, EMS is often summoned when the pain becomes unbearable and the patient desires transport to the emergency department for relief.

Cyclical Vomiting Syndrome

A new phenomenon has occurred over the last several years that is now termed cyclical vomiting syndrome (CVS). It is defined as sudden and repeated episodes of severe nausea, vomiting and abdominal pain, often with associated physical exhaustion. It sometimes associated with headaches, particularly of the migraine type. These episodes can be caused by emotional stress, anxiety, panic attacks, infections and certain foods, and sometimes are associated with a woman’s menstrual cycle. Some cases have no identifiable triggers. These episodes can last for days, preventing the patient from going to work or school. The patient then often recovers and becomes symptom-free. 

Initially there was no apparent cause detected for this condition. However, several studies now associate CVS with repeated and heavy marijuana use. This is particularly true in states in which recreational and medical marijuana use is now legal. 

Treatment of CVS is notoriously difficult. Most patients will be prescribed various antinausea medications. However, these are often ineffective, which can prompt the patient to go to the emergency department or summon EMS.

Diabetic Gastroparesis

Diabetic gastroparesis is a condition seen in diabetics that results in delayed gastric emptying without evidence of any sort of mechanical obstruction of the stomach. It has been estimated that 5%–12% of patients with diabetes will develop diabetic gastroparesis, and it’s more common in type I diabetics.
This condition is characterized by a sensation of fullness after meals, nausea, vomiting and bloating. Associated abdominal pain is also common. As with cyclical vomiting syndrome, diabetic gastroparesis often results in a significant decrease in the patient’s quality of life. 

Treatment of diabetic gastroparesis typically involves the use of typical antinausea medications such as metoclopramide (Reglan), promethazine (Phenergan), prochlorperazine (Compazine), ondansetron (Zofran) and others. Eventually, when these medications fail, the patient will present to the emergency department or call EMS. Most patients with diabetic gastroparesis have found the routine medications carried by EMS are ineffective because of long-term use or other issues. This makes this condition very difficult to treat in both the prehospital and emergency department settings.

Prehospital Treatment

If patients with these conditions don’t generally improve with commonly used medications for pain and nausea/vomiting, new strategies are warranted. 

CPS—Most patients with CPS are taking long-term, often high-dose opiates, and administration of additional opiates in the prehospital setting is often ineffective. Generally evidence-based treatment guidelines do not recommend opiates for the treatment of exacerbations of CPS. Furthermore, many of these patients are enrolled in chronic pain management programs that require them to first obtain permission from their pain medicine physician before receiving opiates or other controlled substances. Given the ongoing opiate epidemic in North America, there is a push to use alternatives as much as possible; thus, we must look at other strategies for helping patients with CPS. 

Ketamine has emerged as fairly effective in the treatment of chronic pain. It’s typically administered intravenously in a subdissociative dose (0.1–0.3 mg/kg). Sometimes a small dose of a benzodiazepine such as midazolam (Versed), lorazepam (Ativan) or diazepam (Valium) is administered to minimize unwanted side effects and help mitigate the emergence phenomena. Other medications such as nitrous oxide, ketorolac (Toradol) and acetaminophen (Ofirmev) may also be of benefit.

Several recent studies have demonstrated that two older medications commonly utilized in EMS may be effective in the treatment of CPS: haloperidol (Haldol) and magnesium sulfate. Both these medications are being used with increasing frequency in modern emergency departments for patients with these conditions.

Haloperidol has been used for years as an adjunctive therapy for patients in hospice and palliative care.^1,2 Although its mechanism of action is unclear, it is believed to be due to blockade of dopaminergic receptors. Recent studies have found the drug effective in the treatment of migraine headaches.^3,4 There is some basic evidence that haloperidol may prevent morphine tolerance and dependence.⁵ Several studies have shown that intravenous magnesium sulfate is also effective in treatment of certain types of pain.^6,7 Its analgesic effects are believed to be related to calcium channel blockade and N-methyl-D-aspartic (NMDA) receptor antagonism.

CVS, diabetic gastroparesis—CVS and diabetic gastroparesis have very similar features. They are characterized by episodes of nausea, vomiting and abdominal pain. With both there is generally a psychological overlay. Many patients with CVS and diabetic gastroparesis are on chronic pain medication therapy and often on chronic antiemetic therapy. As with CPS, these two conditions are notoriously difficult to treat.

There is more evidentiary support for the use of haloperidol in the management of nausea and vomiting associated with CVS and diabetic gastroparesis. It also appears to have some beneficial effect on pain, as well as psychological anxiety associated with these disease processes. Certainly, haloperidol has become the medication of choice for many emergency physicians in the treatment of CVS.^8,9 Often a small dose of diphenhydramine (Benadryl) is given with it to help minimize side effects. Typical dosing includes 25 mg of diphenhydramine followed by 5 mg of haloperidol, both intravenously. The same treatment has also been shown effective in selected cases of diabetic gastroparesis.¹⁰

Follow System Guidelines

There are evolving alternatives to the treatment of pain, nausea and vomiting associated with chronic pain syndrome, cyclical vomiting syndrome and diabetic gastroparesis. The use of haloperidol and magnesium sulfate is based on limited but growing scientific evidence. The lack of other satisfactory medications in the current opioid epidemic has prompted emergency practitioners to seek out such alternatives. 

Always follow your system guidelines when addressing these conditions. Remember, it is not necessary to totally alleviate a patient’s pain. Your goal should simply be to make the pain tolerable. The same holds true for nausea and vomiting: It may not be possible to completely relieve nausea, but you should be able to stop vomiting with the medications provided. 

Consider the medications discussed here when developing EMS system protocols, particularly if you frequently encounter patients with these conditions.  

References

1. Lindqvist O, Lundquist G, Dickman A, et al. Four essential drugs needed for quality care in the dying: a Delphi-study based international expert consensus opinion. J Pallat Med, 2013; 16(1):38–43. 
2. Merskey H. Pharmacologic approaches other than opioids in chronic non-cancer pain management. Acta Anaesthesiol Scan, 1997; 41(1): 187–90.
3. Gaffigan ME, Bruner DI, Watson C, et al. A randomized trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department. J Emerg Med, 2015; 49(3): 326–34.
4. Honkaniemi J, Liimatainen S, Rainesalo S, Sulavouri S. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache, 2006; 46(5): 781–7.
5. Yang C, Chen Y, Tang L, Wang ZJ. Haloperidol disrupts opioid-antinociceptive tolerance and physical dependence. J Pharmacol Exp Ther, 2011; 338(1): 164–72. 
6. Jokar A, Cyrus A, Babaei M, et al. The effect of magnesium sulfate on renal colic pain relief: a randomized clinical trial. Emerg (Tehran), 2017; 5(1): e25.
7. Delavar Kasmaei H, Amiri M, Negida A, et al. Ketorolac versus magnesium sulfate in migraine headache pain management: a preliminary study. Emerg (Tehran), 2017; 5(1): e2.
8. Hickey JL, Witsil JC, Mycyk MI. Haloperidol for the treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med, 2013; 31(6): 1,003.
9. Inayat F, Virk HU, Ullah W, Hussain Q. Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome? BMJ Case Rep, 2017 [e-pub ahead of print].
10. Ramirez R, Stalcup P, Croft B, Darracq MA. Haloperidol undermining gastroparesis symptoms (HUGS) in the emergency department. Am J Emerg Med, 2017 35(8): 1118-1120.

Bryan Bledsoe, DO, FACEP, FAEMS, is a professor in the Department of Emergency Medicine at the University of Nevada, Reno and University of Nevada, Las Vegas schools of medicine. A prominent emergency physician with more than 40 years’ experience in emergency medicine and EMS, he is the author of numerous EMS textbooks, including Paramedic Care: Principles & Practice, Paramedic Emergency Care, Prehospital Emergency Pharmacology, Anatomy and Physiology for Emergency Care and many others.