Dangerous Causes of Nausea/Vomiting Beyond the GI System

Author: Marie J. Murphy, MD (EM Resident Physician, SUNY Downstate Health Sciences Center/Kings County Hospital Center Brooklyn, NY) and Ian S. deSouza, MD (Associate Professor of Emergency Medicine, SUNY Downstate Health Sciences Center/Kings County Hospital Center Brooklyn, NY) // Reviewed by: Marina Boushra, MD; Alex Koyfman, MD (@EMHighAK)

Introduction

Nausea and vomiting are non-specific symptoms of medical illness that can be triggered by peripheral autonomic or central stimuli. In peripheral pathways, gastrointestinal irritation can trigger afferent nerves and produce vagal stimulation to the nucleus tractus solitarius, which will, in turn, respond with signals to induce gastric emptying. Emetic agents in the blood, such as toxins, vestibular stimulators, or chemoreceptive receptor stimulators can also trigger activation of the nucleus tractus solitarius through centrally mediated pathways in the area postrema of the medulla, cerebellum, or cerebral cortex (Figure 1).1,2

Figure 1. Centrally mediated pathways leading to nausea and vomiting

CASE 1

A 70-year-old man who is a former smoker with a past medical history of hypertension, hyperlipidemia, and type 2 diabetes mellitus is brought in by EMS for nausea and vomiting. EMS reports a severe headache, acute in onset just prior to several episodes of vomiting. The blood pressure is 250/180 mm Hg.

Neurologic

Increased intracranial pressure (ICP) causing vomiting can be life-threatening and associated with significant morbidity if not recognized early. In this case, there is a high suspicion of intracranial hemorrhage (ICH). Hypertension is associated with approximately 80% of all intracranial hemorrhages.3 The basal ganglia is the most common site for spontaneous ICH or ICH secondary to hypertension (40%).4

Vomiting is seen in approximately 14.5% of stroke patients and the presence of vomiting is linked with a higher probability of hemorrhagic stroke compared to ischemic stroke (LR 3.0 (95% CI, 1.7-5.5).5,6 In addition to hypertension, other causes of hemorrhagic stroke include arteriovenous malformation (AVM) rupture, aneurysmal rupture, and intracranial mass. Nausea and vomiting are reported in approximately 29–46 % of patients with ICH.7 Although the exact mechanism is unclear, vasodilation and cerebral edema are key factors in the activation of the central vomiting center (Figure 2).

Figure 2. Mechanism of cerebral edema after intracerebral hemorrhage8

Emergency management of patients with cerebral hemorrhage  centers around anticoagulation reversal, blood pressure management, intracranial pressure reduction, glycemic and temperature control, and seizure prevention. Practice patterns are changing, and whether some of the traditional interventions are beneficial remains unclear. Mannitol, traditionally given to treat increased ICP, may not provide any benefit in death or disability outcomes when given within 6 hours of ICH.9 Hypertonic saline may be more effective than mannitol for the treatment of elevated ICP.10

The volume of the hematoma and Glasgow Coma Scale (GCS) score are strong predictors of 30-day mortality and blood pressure management may lower hematoma expansion.11,12 Evidence suggests blood pressure reduction with a nicardipine drip to a target of SBP 140 to 179 mmHg is non-inferior to lower BP targets for the primary outcome of disability and death at 3 months.13,14

CASE 2

 A 55-year-old woman with a past medical history of hypertension and diabetes presents to the ED with nausea/vomiting for 1 hour. She reports sudden-onset interscapular and neck pain and shortness of breath. The blood pressure is 225/150 mm Hg, and the heart rate is 99/min.

 

Cardiovascular

 Cardiovascular causes of nausea/vomiting, including acute coronary syndrome/myocardial infarction and aortic syndromes, can be life-threatening and can be missed/misdiagnosed due to atypical features, particularly in women.15 A systematic literature review and meta-analysis of 27 studies found that female patients with acute coronary syndrome (ACS) had a higher odds of presenting with nausea and vomiting when compared to men (OR 1.64; 95% CI, 1.48–1.82).16

Nausea and vomiting occur frequently in patients with acute myocardial infarction (AMI), although little is known about the mechanism. The signal may originate from a subendocardial or epicardial source. From there, the afferent parasympathetic vagal fibers can stimulate the nucleus tractus solitarius.17

It is hypothesized that the size and location of the infarct can affect the presence of nausea/vomiting. Culić et al (n=1546) studied presenting symptoms in patients with acute anterior, lateral, and inferior infarctions and found an elevated odds ratio of 1.84 (95% CI 1.49–2.28) of nausea in patients with inferior wall MI.18 This may be due to the proximity of the vagus nerve.19

Management & Outcomes

The emergency management AMI is initially supportive in preparation for reperfusion therapy or revascularization.  Consideration should be taken to weight the risks and benefits of the use of antiemetics in AMI. Studies suggest the possibility of cardiotoxicity with D2 receptor antagonists and caution should be taken with serotonin receptor antagonists in patients with prolonged QTc interval due to the potential for cardiac arrhythmias.20,21

CASE 3

A 56-year-old man with a past medical history of CAD, HTN, DM, and CKD4 presents to the ED for nausea and vomiting x 1 hour. The blood pressure is 225/150 mm Hg. The patient is disoriented and has dry mucous membranes.

Renal

Patients with end-stage kidney disease (ESKD) with missed dialysis sessions should obtain a screening electrocardiogram (ECG) for immediate diagnosis of life-threatening electrolyte changes as they are at high risk for complications such as uremia and electrolyte disturbances.

Nausea/vomiting can be a symptom of uremia. The average prevalence of nausea and vomiting in uremia is 36% and 43% respectively.22

Uremia can be seen in patients with persistent GFR< 15mL/min. Accumulated toxins signal the central pathways to induce emesis.23 Decreased excretion of ammonium and hydrogen ions can lead to ​accumulation of acids (i.e., lactic acid, sulfuric acid, hippuric acid) that can result in an anion gap metabolic acidosis.24 Toxins often result in coagulopathies resulting in occult bleeding. To remove these toxins in anuric patients, renal replacement therapy by continuous or intermittent methods is used.

More than 100 toxins have been identified in conjunction with ESKD, with the most common being β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone.25 However, little is known about the pathophysiology of how and why these toxins cause encephalopathy. Water soluble low molecular weight uremic toxins constitute ~ 46% of uremic toxins, whereas protein-bound toxins constitute approximately 25% and are poorly dialyzable.26

CASE 4

An 18-year-old man with no past medical history presents to the ED for nausea/vomiting for 1 hour. He is drowsy and is complaining of upper abdominal pain and thirst. Point-of-Care glucose measurement is greater than 500 mg/dL.

Endocrinologic

Nausea and vomiting are the most common presenting clinical symptoms of diabetic ketoacidosis, estimated to occur in 57% of cases.27 Acute ketosis activates the chemoreceptor trigger zone by central mechanisms.28

Diabetic ketoacidosis (DKA) (Figure 3), is most often precipitated by infection, but other causes include hyperthyroidism, pulmonary embolism, SGLT2 inhibitor use or glucocorticoid use.29

Figure 3. Diabetic ketoacidosis

Patients with severe vomiting are at risk for dehydration and metabolic alkalosis due to the loss of hydrogen ions. Vomiting can also contribute to a total body potassium deficit compounded by the baseline osmotic diuresis and ketosis. Research varies on the best crystalloid for fluid resuscitation in patients with hyperglycemic crises.30,31

Spontaneous pneumomediastinum or Hamman’s syndrome is a rare but possible consequence of severe vomiting (1:7,000 to 1:100,000 of hospital admissions), and cases have been reported in the literature as a complication of DKA.32 The presence of subcutaneous emphysema after severe vomiting should also raise suspicion for Boerhaave’s syndrome, which carries a 40% mortality rate.33

CASE 5

A 23-year-old woman presents to the ED with nausea/vomiting x 1 day. Review of systems negative for vaginal bleeding or vaginal discharge. A urine pregnancy test is positive. Transvaginal ultrasound confirms an intrauterine gestation.

Genitourinary

 

Nausea/vomiting in pregnancy in absence of abdominal pain

 Nausea and vomiting in pregnant patients that result in electrolyte disturbances, weight loss and/or dehydration is known as hyperemesis gravidarum (HG). Although nausea & vomiting is common in pregnancy, the incidence of HG is only 3%.34 HG typically presents within the first 9 weeks of gestation and resolves before 20 weeks. The pathophysiology is thought to be due to increased estrogen levels exerting direct effects on central chemoreceptor triggering zones as well as lower esophageal sphincter relaxation.35

Nausea/vomiting in the presence of abdominal pain

 Following pelvic pain, the most common presenting symptoms in cases of ovarian/testicular torsion are nausea, vomiting, or both, present in approximately 67%, 62.2% and 51.1%, respectively.36Some patients experience cyclic nausea without periods of emesis. An estimated 10%–22% of ovarian torsion occur in pregnant women so this diagnosis should be considered in pregnant patients presenting with vomiting.37

Similarly, the most common presenting complaints for testicular torsion are abdominal pain and vomiting and not all cases will present with acute scrotal pain. The annual incidence of testicular torsion is 4.5 in 100,000 males and can occur at any age, although more common in pediatric patients under 25 years old. 38 Ideally, the diagnosis should be confirmed with ultrasound and surgical exploration initiated within 6 hours to salvage the testicle and prevent necrosis.

Take Home Points

An accurate history of present illness, a thorough review of systems, and a broad differential diagnosis will help identify the underlying cause of nausea/vomiting (Figure 4).

Figure 4. Dangerous causes of nausea/vomiting beyond the gastrointestinal system, summarized by organ system

References

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