Effect Of Exogenous Melatonin on the Incidence of Delirium and Its Association with Severity of Illness in Postoperative Surgical ICU Patients

Dr. Kriti Gupta, MD

Dr. Vipin K. Singh, MD

Dr. Zia Arshad, MD*

Dr. G. P. Singh, MD

*Corresponding Author

Department of Anaesthesiology

King George’s Medical University

Lucknow UP, India 226003

Abstract 

Background: Delirium is common in critically ill intensive care unit (ICU) patients and has been documented in up to 87 percent of patients. Sleep deprivation and delirium have been associated. Alteration of melatonin production has been associated with delirium. Melatonin acts via melatonin receptors present in the suprachiasmatic nuclei (SCN) and promotes sleep by attenuating the wake-promoting signal from the SCN.

Objective: To determine the relationship between exogenous melatonin and the incidence of delirium and its association of with severity of illness, measured in term of APACHE II, procalcitonin level at the time of admission and daily SOFA score.

Patients and Methods:

Design: Randomised placebo-control study.

Setting: the study was conducted in critical care setting in a tertiary level ICU.

Participants: Postoperative patients age between 20-60 years who are going to be ventilated more than 48 hours without any contraindication to enteral medications.

Interventions: Study group received melatonin 5 mg through the enteral route.

Main outcome measures: To determine the effect of exogenous melatonin on the incidence of delirium in postoperative patients who require mechanical ventilation for more than 24 hours. The secondary outcome measures are procalcitonin (PCT) value at admission and disease severity scores like APACHE II and SOFA.

Results: No statistically significant difference was found in admission incidence of delirium or procalcitonin. Age was higher in those patients that developed delirium (p < 0.05).

Conclusions: Although the incidence of delirium is not affected by exogenous melatonin or higher APACHE scores, it had a significant correlation with higher procalcitonin, that in turn indicated an association with delirium and sepsis. It was found that there is increased risk of developing delirium with increasing age.

Key words: delirium, intensive care unit, sedation, melatonin, APACHE II, procalcitonin,

Introduction

Delirium is defined as “A disturbance in attention (i.e., reduced ability to direct, focus, sustain and shift attention) and awareness (reduced orientation to the environment)” (1). Delirium is extremely prevalent in hospitalized patients; it affects 10%–24% of the adult general medicine population and 37–46% of the general surgical population. Delirium has been documented in up to 87 percent of patients in the intensive care unit (ICU) (2). Multiple etiologies have been hypothesized to be causing delirium. Some of these are central cholinergic deficiency, reduced GABA activity, abnormal serotonin and melatonin pathways, cerebral hypo perfusion and neuronal damage due to inflammation (3,4). Acute Physiology and Chronic Health Evaluation II score (APACHE II) and the Sequential Organ Failure Score (SOFA) score have been found to aid in the prediction of delirium in the critically ill.

It has been demonstrated that pattern of secretion and concentration of melatonin are altered in critically ill patients (5). Melatonin release from the pineal gland is also decreased due to surgical stress and hence its potential use in postoperative delirium (6). Sepsis-associated delirium is a cerebral manifestation commonly occurring in patients with other infection-related organ dysfunctions and is caused by a combination of neuroinflammation and disturbances in cerebral perfusion (7). Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients (8).

Melatonin acts via melatonin receptors present in the suprachiasmatic nuclei (SCN) and promotes sleep by attenuating the wake-promoting signal from the SCN (9,10). Bioavailability of melatonin is excellent as demonstrated by supraphysiological level after exogenous supplementation (11).

The Confusion Assessment Method (CAM) is a diagnostic instrument used to screen and diagnose delirium in ICU. The CAM diagnostic algorithm is comprised of four components: (1) an acute (4) an altered level of consciousness. The diagnosis of delirium is based on the presence of both component 1 and 2, and either 3 and 4 (12).

Objective

The primary objective of the study was to determine the efficacy of exogenous melatonin in preventing delirium in postoperative patients admitted in ICU, as well as to compare the outcome by comparing the incidence of delirium and length of ICU stay in two groups. The secondary objective is to determine the association of delirium with severity of illness, which was measured in term of APACHE II and Procalcitonin level at the time of admission and daily SOFA scoring.

Methods

We performed a randomized, placebo-controlled study on postoperative patients admitted in our 20-bed tertiary level ICU. Inclusion criteria included adult postoperative patients requiring mechanical ventilation for more than 48 hours who were able to receive medication by the enteral route. Exclusion criteria included unwillingness to participate; sensitivity or history of allergic reaction to melatonin supplements; pregnancy; paralytic ileus; patients not expected to survive >48 hours; preexisting pathologies including cognitive dysfunction, dementia, psychiatric disorders or sleep disorders; history of head injury, substance abuse or withdrawal; and patients with hearing impairments.

Patients were randomized into two groups of 70 patients each with a sealed envelope randomization method. The study group received melatonin 5 mg via the enteral route at 8 pm every day and the control group received placebo (1 gm lactose powder) through a nasogastric tube until ICU discharge/transfer. APACHE II and procalcitonin (PCT) levels were recorded at admission, and SOFA scores were calculated daily. Delirium preventive measures including decreased light, noise, and regular patient orientation were applied uniformly in both groups. On the day of discharge/transfer the patients were evaluated using the CAM-ICU (Confusion Assessment Method) scale. The patients were categorized as “Delirious” or “Not Delirious” on the basis of the results from the CAM-ICU scale (12). Results were analyzed by comparing the incidence of delirium, length of ICU stay, APACHE II, SOFA Score and PCT value at the time of admission.

Results

A total of 140 adult post-operative patients transferred to the ICU who were ventilated more than 48 hours were evaluated. Table 1 contains the demographics of the study population.

Table 1: Between Group Comparison of Demographic Profile

Mean age of patients enrolled in the study was 38.70±11.56 years. Difference in age of patients in Group A (38.46±11.87) and Group B (38.94±11.33) was not statistically significant.

APACHE II scores did not differ at admission (Table 2).

Table 2: Between Group Comparison of APACHE II Score

Procalcitonin levels did not differ at admission (Table 3).

Table 3: Between Group Comparison of Procalcitonin (ng/ml)

Range of procalcitonin levels of patients of both the groups was 0.2-25.60 ng/ml. Though mean procalcitonin levels of patients of Group B (5.76±6.37 ng/ml) were found to be higher than that of Group A (4.81±6.60 ng/ml) yet this difference was not found to be significant statistically.

Duration of ICU stay was 4 to 27 days. Though mean ICU stay of patients of Group A (9.29±4.57 days) was higher than that of Group B this difference was not found to be significant statistically.

SOFA score of 56 patients of Group A and 55 patients of Group B could be assessed. Median SOFA score of patients of both the groups was 2.00, mean SOFA score of patients of Group A was 2.70±2.20 (range 0-9) while that of Group B was 2.53±1.63. On comparing SOFA score of patients of above two groups, difference was not found to be significant statistically.

CAM ICU score of 111 patients could be assessed. The majority of overall (68.5%) as well as Group A (76.8%) and Group B (60.0%) had negative CAM ICU scores. Though a higher proportion of Group B as compared to Group A had a positive CAM ICU score (40.0% vs. 23.2%), this difference was not found to be significant statistically.

There was no significant difference in the mortality of non-delirious patients.

Patients with delirium as compared to non-delirium had significantly higher values of APACHE-II (20.57±6.26 vs. 18.42±7.14) and significantly higher procalcitonin levels (5.84±6.25 vs. 3.42±6.57 ng/ml).

Table 4: Association of Delirium with Demographic Profile

 

Patients with delirium were found to be older as compared to non-delirium (41.57±9.99 vs. 35.87±11.81). This difference was found to be significant statistically. Proportion of females was higher among delirious as compared to non-delirious patients (54.3% vs. 47.4%), but this difference was not found to be significant statistically.

Delirium was less prevalent in Group A (16.6 percent) than Group B (31.4 percent), although the difference was not statistically significant. Melatonin administration did not significantly affect any of the other outcomes (p>0.05, all comparisons).

Discussion

Delirium is prevalent in all spheres of hospitalization, medical and surgical patients, more prominently in patients admitted to intensive care units. Owing to its multifactorial etiopathogenesis, multiple pharmacological and non-pharmacological methods have been described in various literatures for prevention and treatment of delirium.

Delirium is associated with various complications which may result in unfavorable outcomes. These complications may vary from minor complications like self-extubation, removal of catheters, weaning failure, increase length of ICU stay to increased mortality. Ely and coworkers(13) studied 275 mechanically ventilated medical ICU patients and determined that delirium was associated with a threefold increase in risk for 6-month mortality after adjusting for age, severity of illness, co-morbidities, coma, and exposure to psychoactive medications. The commonest factors significantly associated with delirium are dementia, increased age, co-morbidities, severity of illness, infection, decreased day to day activities, immobilisation, sensory disturbance, urinary catheterization, urea and electrolyte imbalance and malnutrition (14).

Frisk et al. (15) in 2004 conducted a study to assess the biochemical indicators of circadian rhythm of patients admitted in ICUs and found altered secretion patterns and reduction in the urinary metabolite of melatonin, 6-SMT (6-sulphatoxymelatonin). This indicated the possible disruption of this neurohormone in patients admitted in intensive care units. Andersen et al. (16)  concluded that exogenous melatonin could be utilized to alleviate preoperative anxiety in surgical and critical care patients and more importantly, to decrease the emergence of delirium in the early postoperative period. In our study, 140 adult post-operative patients were studied to establish the preventive role of melatonin in delirium. Aghakouchakzadeh et al. (17)  in 2017 conducted a comprehensive review to determine the effect of melatonin on delirium; they concluded that because exogenous melatonin can improve circadian rhythm and prevent delirium, melatonin supplementation could improve or manage delirium in the intensive care unit. Similarly, Yang et al. (18) in their review had found substantial preventative effects of melatonin on delirium .This investigation established a reason for the practice recommendations to recommend melatonergic medications for delirium prevention.

Out of 140 patients that we studied, 29 patients died during the trial, 35 were diagnosed with delirium and 76 had no delirium. Delirium was less prevalent in Group A (16.6 percent) than Group B (31.4 percent), although the difference was not statistically significant. This reduction is similar to the results found by Nishikimi et al. (19) in who found the melatonin agonist to be related to a trend toward shorter ICU stays, as well as significant reductions in the occurrence and duration of delirium in patients admitted to the ICU.

Sepsis and inflammation are important etiologies of delirium. Inflammatory biomarkers (procalcitonin and erythrocyte sedimentation rate) can be predictive of acute brain dysfunction and delirium. Hamza et al.  (20) procalcitonin was significantly higher in their delirious group in univariant (0.9±0.6 vs. 0.4±0.4ng/mL, P<0.001) and multivariate analysis (OR= 35.59, CI (7.73- 163.76)). Similarly, McGrane S et al. (21) conducted a study in 87 non-intensive care unit (ICU) cohorts and found that higher levels of procalcitonin were associated with fewer delirium/coma-free days (odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04). Our study showed similar results with significantly higher procalcitonin levels in patients with delirium than those without delirium (5.84±6.25 vs. 3.42±6.57 ng/ml).

The Acute Physiology and Chronic Health Evaluation II score (APACHE II) provides a classification of severity of disease and is particularly used in the ICU to predict mortality. In our study, APACHE II scores were calculated for each patient at their admission in the ICU. The range of APACHE-II score of patients enrolled was 6 to 38. Patients of Group A and Group B had comparable APACHE-II Score (21.07±8.17 vs. 21.84±7.81). Patients with delirium as compared to non-delirium had higher values APACHE-II scores (20.57±6.26 vs. 18.42±7.14). This was similar to the findings of Hamza SA et. al.(17), who, in their observational study of 90 patients, found not only have higher APACHE scores but also that the APACHE-II scores had significantly high diagnostic performance in discrimination of delirium (AUC = 0.877, P= <0.001).

Another clinically important score is the Sequential Organ Failure Score (SOFA) score used to sequentially assess the severity of organ dysfunction in critically ill patient ,  is an objective score that calculates the number and the severity of organ dysfunction in six organ systems (respiratory, coagulation , liver, cardiovascular, renal, and neurologic). In a prospective cohort study on 400 consecutive patients admitted to the ICU Rahimi-Bashar et al. (22) found the SOFA scores were significantly higher in those with delirium (7.37 ± 1.17) than those without delirium (4.93 ± 1.70). Similarly in our study, SOFA score of patients with delirium (4.49±1.63) was found to be significantly higher than that of non-delirium (1.75±1.37). Hence the elevated SOFA and APACHEII scores in the delirium can assist in identifying at-risk patients for delirium and hence allow interventions to improve outcomes. 

Aging is often associated with a disruption of the normal circadian cycle, which can also result in delirium. Thus, melatonin and its agonist may have a more significant influence on delirium in the elderly than in the young, Abbasi et al. (23) discovered that delirium is uncommon in a relatively young group. Thus, the relatively young age of our study sample and the enhancement of ICU care (such as decreased light, noise, and regular patient orientation) are the primary reasons for our study's low prevalence of delirium. Additionally, we found patients with delirium were older as compared to non-delirium (41.57±9.99 vs. 35.87±11.81).

As previously stated, the potential benefit of exogenous melatonin supplementation in reducing delirium incidence has been evaluated in non-ICU settings as well. While both the Sultan (24) and Jonghe (25) investigations examined whether melatonin may help postoperative patients avoid delirium, the de Jonghe study employed six times the amount of melatonin used in the Sultan study (3 mg versus 0.5 mg, respectively).

We suggest that individuals at risk of developing delirium, such as the elderly, should be investigated in future researches. Also, further studies are required comparing subgroups of medical, surgical, and trauma patients to determine which patients will benefit most from exogenous melatonin administration. Because plasma and urinary levels of melatonin are directly related to its concentration in the central nervous system, we also recommend monitoring melatonin levels in plasma or urine during the study and for follow-up to ascertain which subgroup of patients benefited most from exogenous melatonin supplementation to prevent delirium.

Conclusion

The study demonstrates there is decreased incidence of delirium in the patients who received exogenous melatonin, although this difference was statistically not significant (p=0.057). There was a statistically significant association of age with development of delirium (p=0.015). It has also been observed that the higher procalcitonin levels are associated with increased incidence of delirium (<0.001).

References

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6. Can MG, Ulugöl H, Güneş I, Aksu U, Tosun M, Karduz G, Vardar K, Toraman F. Effects of Alprazolam and Melatonin Used for Premedication on Oxidative Stress, Glicocalyx Integrity and Neurocognitive Functions. Turk J Anaesthesiol Reanim. 2018 Jun;46(3):233-237. [CrossRef] [PubMed]
7. Atterton B, Paulino MC, Povoa P, Martin-Loeches I. Sepsis Associated Delirium. Medicina (Kaunas). 2020 May 18;56(5):240. [CrossRef] [PubMed]
8. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013 May;13(5):426-35. [CrossRef] [PubMed]
9. Sack RL, Hughes RJ, Edgar DM, Lewy AJ. Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sleep. 1997 Oct;20(10):908-15. [CrossRef] [PubMed]
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11. Bellapart J, Appadurai V, Lassig-Smith M, Stuart J, Zappala C, Boots R. Effect of Exogenous Melatonin Administration in Critically Ill Patients on Delirium and Sleep: A Randomized Controlled Trial. Crit Care Res Pract. 2020 Sep 23;2020:3951828. [CrossRef] [PubMed]
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13. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. [CrossRef] [PubMed]
14. Ahmed S, Leurent B, Sampson EL. Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing. 2014 May;43(3):326-33. [CrossRef] [PubMed]
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Cite as: Gupta K, Singh VK, Arshad Z, Singh GP. Effect Of Exogenous Melatonin on the Incidence of Delirium and Its Association with Severity of Illness in Postoperative Surgical ICU Patients. Southwest J Pulm Crit Care Sleep. 2022;25(2):7-14. doi: https://doi.org/10.13175/swjpcc030-22 PDF 

Pediculosis As a Possible Contributor to Community-Acquired MRSA Bacteremia and Native Mitral Valve Endocarditis

Ali A. Mahdi MD, Charis Tjoeng DO, Vishal Patel MD, Serap Sobnosky MD

Dignity Health St Mary Medical Center

Department of Internal Medicine

Long Beach, California USA

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a known cause of infective endocarditis. In this case report, we describe a patient with community-acquired MRSA bacteremia and subsequent mitral valve endocarditis. This patient was noted to be without commonly recognized risk factors for MRSA bacteremia, thus her likely source was skin colonization, with skin trauma facilitated by pediculosis infestation.

Case Presentation

An elderly woman was brought to the Emergency Department after being found down. A bystander called EMS after finding her lying on the ground next to a pool of emesis. Per EMS, the patient was found to have pinpoint pupils with Glasgow Coma Scale (GCS) 4-1-4, with only minimal improvement with a dose of naloxone. After admission she was noted to be afebrile, with a III/VI systolic murmur and an extensive infestation of lice in her hair. Urine toxicology screen was negative. CT radiography of her head was negative for acute intracranial pathology, with chronic ischemic changes. Blood cultures were drawn from two peripheral sites, but as the patient was afebrile without leukocytosis, she was not started on antibiotics. Her identity was later confirmed, and she was noted to be 72 years old with a history of homelessness. She had previously denied a history of IV drug abuse or previous surgeries, and was not noted to be hospitalized recently.

On the second day of hospitalization, her mentation improved, and she was described as coherent on exam. However, she became febrile to maximum temperature 38.5° C with a new leukocytosis to 14,500. Two of two blood cultures, drawn on admission, resulted in gram positive cocci with clusters, and she was started on empiric vancomycin therapy. The initial two blood cultures, as well as two repeat blood cultures later speciated to methicillin-resistant Staphylococcus aureus (MRSA). MRSA nares swab results were negative. However, as the patient was noted to have persistent pediculosis infestation, a possible source of MRSA bacteremia was skin colonization introduced to her bloodstream through excoriations. An infectious disease specialist was consulted, who recommended a transthoracic as well as a transesophageal echocardiogram.

Transthoracic echocardiography (TTE) revealed a moderate mobile vegetation on the posterior mitral valve leaflet (Figure 1A), as well as severe mitral regurgitation (Figure 1B).

Figure 1. Transthoracic echocardiography showing large vegetation on posterior leaflet of mitral valve (A) and severe mitral regurgitation resulting from large vegetation (B).

Left ventricular ejection fraction was reported to be 55-60%, with no other vegetations noted. On day five of hospitalization, the patient underwent transesophageal echocardiography (TEE), which revealed large vegetation on the posterior leaflet measuring 2.5 x 0.8 cm (Figure 3) causing severe mitral regurgitation (Figure 2).

Figure 2. Transesophageal echocardiography redemonstrating large vegetation on mitral valve (red arrow), measuring 2.5 x 0.8 cm.

A cardiothoracic surgery evaluation was obtained for mitral valve replacement, and she was deemed a surgical candidate.

In preparation for surgical intervention, cardiac catheterization was performed, which revealed no coronary artery disease. The patient’s pediculosis was noted to persist despite three topical treatments and two doses of oral ivermectin, and an additional dose of ivermectin was planned. Two repeat blood cultures resulted in no growth, and the patient was pending cardiothoracic surgery. However, on the day of surgery, the patient elected to leave against medical advice (AMA) despite extensive counseling. She had received 18 days total of IV vancomycin.

Discussion

MRSA continues to cause significant morbidity and mortality both in healthcare and community populations. S. aureus bacteremia can often cause complications, most concerning infective endocarditis, osteomyelitis, and sepsis. Incidence of community-acquired MRSA bacteremia, including healthcare-associated cases, has increased in recent years, surpassing rates of hospital-acquired infections globally (1-3). MRSA colonization increases the risk of MRSA infections and bacteremia; in a study of 29371 hospitalized patients, MRSA-colonized (per nasal swab) patients were 19.89 times more likely to develop bacteremia than non-colonized patients (4). Sites of S. aureus colonization include the nares, nasopharynx, skin, wound sites, and vascular catheters. Once colonized, traumatic injury or disruption can facilitate invasion of S. aureus into deeper structures of the skin, which can in turn lead to bacteremia.

There have been no documented cases of pediculosis as a contributor to MRSA bacteremia. However, lice have been identified as vectors for several pathogens, including Bartonella quintana, Rickettsia prowazekii, and Borrelia recurrentis (5). In particular, pediculosis has been shown to be associated with B. quintana seroconversion and bacteremia in a study of homeless individuals (6). B. quintana,is a gram negative bacteria transmitted by responsible for trench fever in World War I, during which it was transmitted by lice. More recently, it has been reported to cause bacillary angiomatosis, acute and chronic bacteremia, and endocarditis, with homeless persons and individuals with alcoholism at significant risk (7). Bartonella species including B. quintana have recently been described as emerging causes of culture-negative endocarditis (8). Notably, one case report documents a patient with a history of pediculosis, found to have culture-negative endocarditis. TEE revealed a 2.5 x 0.9 cm vegetation on the mitral valve and several small vegetations on the aortic valve. Serology was positive for both B. quintana and B. henselae, and rRNA sequencing confirmed B. quintana infection of both valves (9).

On TEE, our patient was shown to have a large vegetation on the mitral valve, measuring 2.5 x 0.8 cm in diameter. Given the high risk of embolization and severe mitral, valve replacement surgery was highly recommended. Per ID specialist, a six-week course of antibiotics was also recommended for complicated bacteremia. Unfortunately, the patient left against medical advice (AMA) before surgical intervention and before an appropriate duration of antibiotics.

The source of this patient’s bacteremia was initially unclear, as she did not have common risk factors for MRSA bacteremia. She denied IV drug use, was not recently admitted to a hospital or nursing facility, did not have any chronic conditions or prosthetic devices, and was found to have a negative MRSA nares swab. Thus, her source of infection was possibly skin colonization with MRSA, with introduction into her bloodstream facilitated by excoriations due to persistent pediculosis infestation. She was noted to have a significant amount of lice despite several topical and oral medications, and left AMA before completing a three-dose course of ivermectin.

Conclusion

In this case report, we describe a patient with community-acquired MRSA bacteremia and subsequent mitral valve endocarditis. In the absence of common risk factors, her likely source of infection was considered to be skin colonization, with skin barrier disruption from excoriations due to pediculosis.  

References

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Cite as: Mahdi AA, Tjoeng C, Patel V, Sobnosky S. Pediculosis As a Possible Contributor to Community-Acquired MRSA Bacteremia and Native Mitral Valve Endocarditis. Southwest J Pulm Crit Care Sleep. 2022;25(5):74-7. doi: https://doi.org/10.13175/swjpccs017-22 PDF

April 2022 Critical Care Case of the Month: Bullous Skin Lesions in the ICU

Margaret Wat MD PhD, Jawad Bilal MD, Martin Chacon MD, Stephen Klotz MD, and Janet Campion MD

University of Arizona College of Medicine-Tucson

Tucson, AZ USA

History of Present Illness: A 29-year-old woman with past medical history of mixed connective tissue disease [lupus predominant], prior pulmonary embolism complained of a 2-week history of nonproductive cough. The cough began after her son was diagnosed with respiratory syncytial virus (RSV). Symptoms progressively worsened and now she is admitted from the  emergency department (ED) with generalized weakness and progressive shortness of breath. Earlier in the day at an outside hospital, she tested positive for RSV, negative for COVID-19 and had normal O2 saturations and was discharged home. She has not received COVID-19 vaccine. Symptoms progressed, 911 called and in the ED, she was found to have temperature = 104°F, SpO2 = 64% on room air, and fasting blood sugar in the 40s. She was lethargic with visible respiratory distress and unable to answer questions.

Past Medical History:

• Mixed connective tissue disease [features of systemic lupus erythematosus, rheumatoid arthritis, polymyositis, scleroderma]
• Membranous lupus nephritis [class V]
• History of pulmonary embolus
• Posterior intracranial artery infarct with venous sinus thrombosis in February 2020
• Hypertension
• Recent septic shock due to pneumococcal bacteremia 2 months prior to admission
• Post-op C section

Medications:

• Atovaquone 750 mg BID
• Eliquis 5 mg BID
• Fluconazole 150 mg Q 72h
• Hydroxychloroquine 200 mg daily
• Nifedipine 30 mg daily
• Pantoprazole 40 mg BID
• Prednisone 5 mg daily
• Vitamin D3 2000 IU daily
• Albuterol PRN SOB
• Ferrous sulfate 325 mg daily
• Losartan 25 mg daily

Social History and Family History

• Married, nonsmoker, rare social ethanol use, no recreational drug use
• Father with hypertension, mother with autoimmune disease

Physical Examination

• T = 40°C, heart rate = 130 beats/min, respiratory rate = 28 breaths/min, BP = 100/61 mm Hg, SpO2 = 95% on 100% nonrebreathing mask, BMI = 24
• General: Lethargic well-nourished young woman unable to answer questions, accessory respiratory muscle use
• HEENT: Dry mucosa, no scleral icterus, injected conjunctiva
• Pulmonary: No audible wheeze, crackles, rhonchi
• CV: Tachycardic, regular, no murmur
• Abd: Tender bilateral upper quadrants, nondistended, no HSM
• Neurological: Moving extremities but unable to follow commands, CN grossly intact
• Psychiatric: Unable to assess, mentation/mood normal earlier in day per her husband
• Extremities: Warm with mottled UE and LE digits, scattered areas of purpura (Figure 1)

Figure 1. Photographs of extremities taken during day 1 and 2 in the ICU.

With this patient's presentation, what is the most likely cause of the purpura? (Click on the correct answer to be directed to the second of six pages)

1. Angioinvasive fungal infection
2. Thrombotic related to cryoglobulinemia
3. Septic emboli
4. Thrombosis from disseminated intravascular coagulation (purpura fulminans)
5. Depositional vessel disease from calciphylaxis

Cite as: Wat M, Bilal J, Chacon M, Klotz S, Campion J. April 2022 Critical Care Case of the Month: Bullous Skin Lesions in the ICU. Southwest J Pulm Crit Care Sleep. 2022;24(4):57-61. doi: https://doi.org/10.13175/swjpccs014-22 PDF

Leadership in Action: A Student-Run Designated Emphasis in Healthcare Leadership

Morcel Hamidy, BS¹

Kishan Patel, BS¹

Sonul Gupta, BS¹,

Manparbodh Kaur, BS¹

Jordan Smith, MD²

Haeli Gutierrez, BS¹

Mohamed El-Farra, MS¹

Natalie Albasha, BS MS¹

Priya Rajan, BA¹

Secilia Salem, BS¹

Somiya Maheshwari, BS¹

Kendrick Davis, PhD³

Brigham C Willis, MD, MEd⁴

¹Medical Student, UC Riverside School of Medicine

²Resident, Loma Linda Pediatric Residency Program

³Associate Dean of Assessment and Evaluation, UC Riverside School of Medicine

⁴Senior Associate Dean of Medical Education, UC Riverside School of Medicine

Abstract 

Background: Throughout medical school students are exposed to a variety of fields within medicine, but structured leadership and teaching opportunities are limited. There is a need for more training to prepare students of all backgrounds to be future leaders in all healthcare realms, especially critical care medicine, in order to address the lack of diversity seen in leadership positions.

Methods: Implemented entirely by students with faculty guidance, the Kern model was applied to develop a student-run longitudinal Designated Emphasis in Healthcare Leadership. This program was implemented at a medical school leading the nation in creating opportunities for diverse and underrepresented groups in medicine. Students are involved in structured leadership lectures, projects, and mentorship, and there is an emphasis on learning by doing. A survey was sent out to all present and past student participants to assess its acceptability and effectiveness.

Results: A post-participation survey found that a total of 96% of participants identified themselves as healthcare leaders, felt confident leading a team, and felt comfortable working with a diverse team. Further, 96% of participants agreed or strongly agreed they would recommend the program to other medical students. Qualitative feedback revealed that participants felt they learned how to “apply leadership skills to the healthcare setting” and were provided an “environment to grow and practice vital leadership skills that will help [them] be effective clinicians.”

Conclusions:  Our initial research shows that introducing a longitudinal leadership program into Medical Education may allow participants to start developing personal and professional leadership qualities. The program is well-received by the students and preliminary data shows that there may be increase in leadership capabilities when participating in this program. Such a program can enable future healthcare providers to become leaders in their own fields, so that they can hone interpersonal communication skills, bridge the gap of representation in leadership positions, and lead teams effectively.

Introduction 

Responding to critical care emergencies requires effective coordination and management of multiple healthcare providers. Hence, leadership skills and multidisciplinary teamwork are recognized as significant curricular milestones and learning objectives for pulmonary and critical care medicine (PCCM) learners by the Accreditation Council for Graduate Medical Education (ACGME) (1). Effective communication and leadership acumen are critical non-medical aspects of successful patient management in the intensive care unit (ICU), often leading to increased performance and improve patient outcomes (2,3). Despite this, leadership training opportunities are variable from program to program, with no clear consensus on the components of effective leadership curricula. As a result, there are no guidelines on a standardized leadership curricula in critical care medicine or undergraduate medical education (4,5).

There has been some progress within the undergraduate medical education community to integrate healthcare leadership into medical curricula. The number of MD-MBA dual degree programs grew by 25% from 2011 to 2012 alone (6). However, only a fraction of medical schools provide students with opportunities for medical leadership training, with courses typically being elective (7). The Association of American Medical Colleges (AAMC) stated that graduating medical students should learn “leadership skills that enhance team functioning, the learning environment, and/or the health care delivery system” (8). In 2015, a survey showed that 46 out of 88 allopathic medical schools had some form of leadership curriculum.7,9 The curricula of these schools included: mentoring programs (65.1%), dual degree programs (54.5%), workshops (48.8%), seminar/lecture series (41.9%), courses (41.9%), or single seminars (18.6%). However, despite the rise in importance of leadership education, only 19% percent of those institutions offered a longitudinal leadership education throughout medical school (9).

There is also a need to address inequities in healthcare leadership. A recent AAMC report on diversity and inclusion in Medical School Deans found that only 11% of US Medical School Deans are underrepresented in medicine (URiM). Further, the report highlighted that this number has been stagnant over the past 30 years, growing from 7% in 1991 to only 11% in 2020 - an alarming trend highlighting the barriers to ensuring appropriate representation in our healthcare leadership positions (10). The UC Riverside School of Medicine (UCR SOM) has been at the forefront of bridging the gaps in inequities. It was recently named the sixth most diverse medical school in the nation based on metrics of student enrollment of underrepresented in medicine background, percent of graduates practicing in primary care and rural medicine, and percent of graduates eventually working in underserved regions (US News). The UCR SOM led these metrics with an outstanding 34.1% student population from underrepresented in medicine backgrounds. Hence, programs led at the UCR SOM reflect a growing trend attempting to bridge gaps in leadership representation (11).

To address these needs, we created a student-run leadership program using the Kern Six-Step Model highlighting competencies considered fundamental to leadership development (12). The goal was to develop longitudinal leadership training at the undergraduate medical education level to train future providers to have confidence and readiness to manage interdisciplinary teams in complex medical situations, such as the ICU. As a student-run program with support of faculty, we report a detailed description of the Healthcare Leadership Program (HLP) in the hopes that it may be helpful to implement a standardized leadership training model at other institutions.

Methods

To implement the Healthcare Leadership Program (HLP) as a Designated Emphasis within Medical Education, students met with a faculty mentor to establish topics and activities (Appendix A and Appendix B) that met credit requirements set by the School of Medicine. A leadership structure (Appendix C) that focused on student oversight was then established. In addition to the lecture and workshop curriculum, students were expected to actively participate in mentorship and projects. This amounted to a total of 30 units distributed across the four-year program, allowing for 320 contact hours with 304 required hours to obtain a Designated Emphasis in Healthcare Leadership. Upon completion, students are given a distinction on their Medical Student Performance Evaluation (MSPE) and their diplomas. Selection of students was done through an application (Appendix D) and interview process.

Special attention was taken to accept students from a variety of diverse backgrounds in order to help bridge inequities currently seen in healthcare leadership. This was done through an interviewing process and holistic review of applicants. The number of students increased annually as the program grew stronger and obtained more resources. The initial cohort started with 8 total students throughout all medical school years, and currently the number of students per year is capped at 10 students per year due to restraints in educational resources available. The current attrition rate is 4% of students deciding to not continue with the program.

For the first-year curriculum (Appendix A), students were expected to complete a minimum of 14 hours. The aim of the year was to build a strong leadership foundation by teaching leadership fundamentals, helping students understand their own strengths, and how to effectively collaborate with peers. Activities included students learning about their own strengths and weaknesses through a formalized StrengthsFinder assessment. Students were also taught to improve efficiency and reduce waste in organizations through LEAN/6 Sigma White and Yellow Belt training. Further, guest speakers supplemented learning by teaching topics including communication skills, leading meetings, conflict resolution, and networking. A full list of topics taught during the 2018-2019 academic year are included in Appendix A.

For the second-year curriculum (Appendix B), students were expected to complete a minimum of 10 hours. During the second-year, we focused on growing students into healthcare leaders. The curriculum focused on healthcare leadership and medical management by teaching the most common and relevant principles from Masters in Business Administration (MBA), Masters in Public Policy (MPP), and Masters in Public Health (MPH) programs. The goals and objectives for the students were taught through mixed media including online lectures, lecturer workshops, and discussions with community leaders. A full list of topics taught during the 2019-2020 academic year are included in Appendix B.

For the third and fourth-year curriculum, the focus was to have student leaders practice what they learned in the first two years and apply it to the professional world. For the third and fourth year, students engage in selectives. Selectives are 3 weeks during the third year totaling 12 units for 120 hours and 4 weeks during the fourth year totaling 16 units for 160 hours. The selective was comprised of five different parts including hands-on experience in a clinical setting, observation of current practices, formal report of possible improvements, resource summaries, and continued participation in mentorship programs. Selectives are self-created by HLP students, with the help of HLP board members and faculty advisors. Third and fourth-year students were assessed via a form included in Appendix E.

It is important to note that in this student-run program, the students themselves were responsible for coordinating and executing the lectures. The majority of lectures were given by students from previous cohorts, and this cycle continued where each cohort was responsible for educating the following cohort. Occasionally, guest lecturers were asked to come and teach the students. The material was saved and uploaded to an online drive for the following years to be able to access in order to maintain fidelity of the curriculum.

Outside of the structured curriculum, each student is required to work on a project of their choice in the first two years of medical school. The goal of this requirement is to allow student leaders to gain experience in navigating bureaucracies, innovation, and building teamwork and networking skills through hands-on experience on a topic they feel passionate about. Students pay special attention to initial measurements to identify baseline data, implementation of intervention, and collecting results, with an ultimate goal of publishing the project. At the end of the project, students make a formal presentation to the HLP Board and School of Medicine Leadership.

This project also prepares students for their fourth-year capstone projects. During this time students have the opportunity to spend four weeks at a clinical site, observing current operating procedures in an effort to identify strengths that they can employ in their future practice, and weaknesses that could be improved. Students are assigned a faculty advisor and are responsible for designing one intervention aimed at improving efficiency and reducing waste, based on their observations. After incorporating feedback, students have the opportunity to implement their proposed project at the site.

HLP is made up of general members and executive board members, all exclusively students. Appendix C highlights the structure of the executive board which is made up of three tiers. The first tier includes the Member Development Officer, Operations Officer, Medical Education Officer, and Community Relations Officer who are primarily responsible for first year HLP general members. The second tier consists of the Chief Innovation Officer, Chief Operations Manager, Chief Medical Education Officer, and Chief Community Relations Officer and are responsible for the second year HLP students in addition to managing the officers in tier one. In tier three, the Chief Executive Officer oversees the rest of the officer board and manages communication with the School of Medicine Leadership and administration. Finally, the HLP Alumni Advisory Board is a network of graduated HLP medical students who offer guidance and support to the executive board. The specific responsibilities of the executive board positions can be found in Appendix C.

In addition to lectures and workshops, students are expected to participate in formal mentorship. Mentorship pairing occurred in the first year, after students shared a biography of their past experiences, interests, and passions. The Community Relations Officers met with each individual student to discuss their interests and career aspirations. The Officer then works with the rest of the Executive Board and Advisors in helping place students with the right mentor. Students in the program are connected with local CEO’s, CMO’s, Dean’s, Business Specialists, and Residency Program Directors. The mentor-mentee relationship is cultivated over the duration of the medical student’s training, as the students finalize their career path and passion projects.

Aligning with Kern Model Step 6: Evaluation and Feedback (12), surveys were sent out periodically to evaluate the effectiveness of the curriculum. A survey was sent out regarding all first-year lectures which was completed by the entire cohort (Appendix F). Results of this survey helped plan the first-year lectures for the next cohort. A survey was also sent out to assess the effectiveness of the program as a whole, which was completed by the entire HLP Cohort (Appendix G). The Institutional Review Board (IRB) did not review our project as it was conducted for the purposes of course improvement and evaluation, and therefore, IRB review was not required.

Results

The program was implemented with a total cohort of 25 participants. A post-participation survey (Appendix G) was sent to participants to understand their personal growth and learning throughout the program. Participant responses to various questions detailing their healthcare leadership education through HLP was noted using a questionnaire using a 1 through 5 scale, with 1 indicating very low, 2 indicating low, 3 indicating neutral, 4 indicating high, and 5 indicating very highly. Results are shown in Table 1.

Table 1. Participant questionnaire responses to various questions detailing their healthcare leadership education through HLP was noted using a questionnaire using a 1 through 5 scale, with 1 indicating very low, 2 indicating low, 3 indicating neutral, 4 indicating high, and 5 indicating very highly. The entire cohort of 25 students was surveyed.

Participants were also asked to note if they strongly disagree, disagree, neutral, agree, or strongly agree with statements reflecting on their personal capabilities as a leader. Results are included in Figure 1.

Figure 1. Results for the question “how strongly do you agree with the following statements” pertaining to personal leadership capabilities. The entire cohort of 25 students was surveyed. The y-axis represents the number of students that agree with the above statements.  

All 25 students of the cohort were surveyed for this data collection.

A total of 96% of participants agreed or strongly agreed that they identified themselves as a healthcare leader, felt confident leading a team, and felt comfortable working with a diverse team. Further, 96% of participants agreed or strongly agreed they would recommend the program to other medical students.

Students were given the opportunity to share comments throughout the survey. Participants felt they learned how to “apply leadership skills to the healthcare setting” and were provided an “environment to grow and practice vital leadership skills that will help [them] be effective clinicians.” Other comments highlight community building within HLP, such as “I have been able to meet people who are very much like-minded. That in itself is very nourishing.” Anecdotal evidence also suggests that students value HLP’s curriculum as it “prepares students for professional goals” and allows for “hands-on experience in grant writing and research.”

A prevailing theme among participants was that students enjoyed the autonomy of the program to explore their interests and passions. Students stated that, “Individuals lead in different manners and to only provide one cookie-cutter set of leadership instruction would be limiting to the diverse members of HLP” and that they enjoy the “flexibility to pursue anything [they] want under the large umbrella of leadership.”

However, with this flexibility and fluidity of the program, came some critiques as well. One student noted that, “The curriculum seems scattered to me … while it is good to learn a diversity of information, a lack of direction leaves the curriculum feeling disorganized.” Another recommendation was the desire for more networking opportunities with faculty and other students: “A lot of our speakers are Faculty, and I think we can learn some new perspectives and tools if we branch beyond our networks.” The current model of HLP was that the second, third, and fourth-year medical students help network to find mentors for the first-year students. Some students noted that perhaps we should, “encourage the first years to do so by hosting a seminar-like session where we could encourage networking [because] by doing it for them, we are limiting their own involvement and learning.”

The results of the Healthcare Leadership Program were also measured by the success of the projects that have started within the program. The dual nature of students being facilitators as well as learners was unique to HLP, as students played an active role in their education. Hands-on experience was integral and allowed students to participate in passion-driven specific ventures. 

For example, members of HLP participated in a Quality Improvement project at a Student-Run Free Clinic. After first observing the clinic flow, HLP members came together to brainstorm ways to optimize clinic efficiency and proposed a number of interventions. The team then presented changes to the Board of the Free Clinic, received approval, and implemented the interventions. This project improved the workflow and optimized efficiency of the Free Clinic, resulting in a statistically significant decrease in patient door-to-door times. Students then published this data at the American Medical Association Research Symposium December 2020 (Appendix H).

Discussion

Many demanding specialties, particularly PCCM, require extensive leadership skills. Despite this, most medical schools lack any formal, longitudinal leadership training integrated into the curriculum9. One possible reason for the lack of leadership curricula may be that there is a lack of consensus on what leadership competencies should be emphasized (13,14). Many have proposed a curriculum that focuses on emotional intelligence, self-reflection, and communication skills to be among the most effective (13,15,16,17). Our program encourages these skills via lectures as well as hands-on projects where they put leadership skills learned into practice in interdisciplinary clinical settings. Our program is focused on drawing out the passions and interests possessed by medical students, and teaching them to sharpen their leadership skills to be effective leaders. HLP is focused on a “learning-by-doing” model (17), where students are first equipped with the tools, they need to be effective and then allowed to practice these skills in projects they care about. 

HLP is an innovative Designated Emphasis that has been ongoing for four years. As a student led organization, the development has been flexible and adaptable to student needs and interests, with guidance by appropriate mentors for different topics. Our preliminary data shows HLP to be well received by the current cohort, in which 96% of students identified themselves as a healthcare leader. Further, 96% of participants agreed or strongly agreed they would recommend the program to other medical students. HLP is a dynamic, ever-changing program, where we utilize the innate skills and passions of use students to constantly reshape the curricula to fit the needs of the students in that cohort. Feedback is encouraged in every step of the program, as all students share the growth-mindset ideology of utilizing feedback to better the program.

As a new, developing program, HLP has some limitations. The program covers the most common leadership positions, but it does not cover all possible avenues of leadership, and some of the more unique positions may not be explored as in depth. Another limitation is that due to current resources, only a limited number of applicants can be accepted into the Designated Emphasis. In particular, one of the most limiting resources is available and engaged mentors. A strong and significant network of physician leaders is imperative for the program’s success.

It is our hope that HLP can be used as a template and be incorporated into the medical education curriculum at other schools as a Designated Emphasis, Selective, Thread, or Interest Group. The organized curriculum can be used as a guided lecture series throughout medical school but can also be utilized in PCCM residency programs. The program gives great exposure to what different leadership programs may look like, including Master’s and other graduate programs, and can be used as a guide for medical students and residents to focus their interests. Additionally, the HLP will create opportunities for building strong leadership skills early on that can help prepare future PCCM physicians of tomorrow.

Acknowledgements

We would like to acknowledge the founders of the Healthcare Leadership Program at UC Riverside School of Medicine: Matt Gomez MD, Nekisa Haghighat MD, MPH, Frances Tao MD, MPH, and Cassidy Lee MS, MPP, along with the help of their faculty advisor, Paul Lyons MD. We would also like to thank Ms. Elisa Cortez for her help with literature review.

References

1. Fessler HE, Addrizzo-Harris D, Beck JM, Buckley JD, Pastores SM, Piquette CA, Rowley JA, Spevetz A. Entrustable professional activities and curricular milestones for fellowship training in pulmonary and critical care medicine: report of a multisociety working group. Chest. 2014 Sep;146(3):813-834. [CrossRef] [PubMed]
2. Schmutz J, Manser T. Do team processes really have an effect on clinical performance? A systematic literature review. Br J Anaesth. 2013 Apr;110(4):529-44. [CrossRef] [PubMed]
3. Hunziker S, Johansson AC, Tschan F, Semmer NK, Rock L, Howell MD, Marsch S. Teamwork and leadership in cardiopulmonary resuscitation. J Am Coll Cardiol. 2011 Jun 14;57(24):2381-8. [CrossRef] [PubMed]
4. Clyne B, Rapoza B, George P. Leadership in Undergraduate Medical Education: Training Future Physician Leaders. R I Med J (2013). 2015 Sep 1;98(9):36-40. [PubMed]
5. Rosenman ED, Shandro JR, Ilgen JS, Harper AL, Fernandez R. Leadership training in health care action teams: a systematic review. Acad Med. 2014 Sep;89(9):1295-306. [CrossRef] [PubMed]
6. Goyal R, Aung KK, Oh B, Hwang TJ, Besancon E, Jain SH. AM last page. Survey of MD/MBA programs: opportunities for physician management education. Acad Med. 2015 Jan;90(1):121. [CrossRef] [PubMed]
7. Neeley SM, Clyne B, Resnick-Ault D. The state of leadership education in US medical schools: results of a national survey. Med Educ Online. 2017;22(1):1301697. [CrossRef] [PubMed]
8. AAMC organization. Core entrustable professional activities for entering residency. https://www.aamc.org/system/files/c/2/482194-epa4toolkit.pdf. Accessed October 21, 2021.
9. Richard K, Noujaim M, Thorndyke LE, Fischer MA. Preparing Medical Students to Be Physician Leaders: A Leadership Training Program for Students Designed and Led by Students. MedEdPORTAL. 2019 Dec 13;15:10863. [CrossRef] [PubMed]
10. U.S. medical school deans by Dean type And Race/ethnicity (URIM vs. non-URiM). AAMC. https://www.aamc.org/data-reports/faculty-institutions/interactive-data/us-medical-school-deans-trends-type-and-race-ethnicity (accessed March 21, 2022)..
11. Morse R, Castonguay A, Vega-Rodriguez, J, Brooks E, Hines K. Most Diverse Medical Schools. https://www.usnews.com/best-graduate-schools/top-medical-schools/medical-school-diversity-rankings. Published March 30, 2020 (accessed March 21, 2022).
12. Thomas PA, Kern DE, Hughes MT, Chen BY. Curriculum Development for Medical Education: A Six-Step Approach. Baltimore, MD: Johns Hopkins University Press;2015:1-300.
13. Stoller JK. Developing physician-leaders: a call to action. J Gen Intern Med. 2009 Jul;24(7):876-8. [CrossRef] [PubMed]
14. Lobas JG. Leadership in academic medicine: capabilities and conditions for organizational success. Am J Med. 2006 Jul;119(7):617-21. [CrossRef] [PubMed]
15. Stoller JK. Developing physician-leaders: key competencies and available programs. J Health Adm Educ. 2008 Fall;25(4):307-28. [PubMed]
16. Mintz LJ, Stoller JK. A systematic review of physician leadership and emotional intelligence. J Grad Med Educ. 2014 Mar;6(1):21-31. [CrossRef] [PubMed]
17. Reese, H. W. (2011). The learning-by-doing principle. Behavioral Development Bulletin. 2011;17(1):1-19. [CrossRef]

Cite as: Hamidy M, Patel K, Gupta S, Kaur M, Smith J, Gutierrez H, El-Farra M, Albasha N, Rajan P, Salem S, Maheshwari S, Davis K,  Willis BC. Leadership in Action: A Student-Run Designated Emphasis in Healthcare Leadership. Southwest J Pulm Crit Care Sleep 2022;24(3):46-54. doi: https://doi.org/10.13175/swjpccs 007-22 PDF

MSSA Pericarditis in a Patient with Systemic Lupus Erythematosus Flare

Antonious Anis MD

Marian Varda DO

Ahmed Dudar MD

Evan  D. Schmitz MD

Saint Mary Medical Center

Long Beach, CA 90813

 

Abstract

Bacterial pericarditis is a rare yet fatal form of pericarditis. With the introduction of antibiotics, incidence of bacterial pericarditis has declined to 1 in 18,000 hospitalized patients. In this report, we present a rare case of MSSA pericarditis in a patient that presented with systemic lupus erythematosus flare, which required treatment with antibiotics and source control with pericardial window and drain placement.

Abbreviations

• ANA: Anti-nuclear Antibody
• Anti-dsDNA: Anti double stranded DNA 
• IV: intravenous
• MSSA: Methicillin-sensitive staphylococcus aureus
• SLE: systemic lupus erythematosus 
• TTE: Transthoracic Echocardiogram

Case Presentation

History of Present Illness

31-year-old female with history of SLE, hypertension and type 1 diabetes mellitus presented with several days of pleuritic chest pain.

Physical Examination

Vitals were notable for blood pressure 204/130. She had normal S1/S2 without murmurs and had trace bilateral lower extremity edema.

Laboratory and radiology

Admission labs were notable for creatinine of 1.8, low C3 and C4 levels, elevated anti-smith, anti-ds DNA and ANA titers. ESR was elevated at 62. Troponin was normal on 3 separate samples 6 hours apart. CT Angiography of the chest showed moderate pericardial effusion (Figure 1).

Figure 1. CT Angiography of the chest on admission with moderate pericardial effusion (arrows).

Transthoracic echocardiography (TTE) showed a moderate effusion, but no tamponade physiology.

Hospital Course

Given the ongoing lupus flare, pleuritic chest pain, elevated ESR, normal troponin and pericardial effusion, the patient’s chest pain was thought to be caused by acute pericarditis secondary to SLE flare. The patient was treated with anti-hypertensives, though her creatinine worsened, which prompted a kidney biopsy, that showed signs of lupus nephritis. The patient was treated with methylprednisolone pulse 0.5 mg/kg for three days, then prednisone taper. Her home hydroxychloroquine regimen was resumed. The patient became febrile on hospital day 15 and blood cultures were obtained. These later revealed MSSA bacteremia, which is thought to be secondary to thrombophlebitis from an infected peripheral IV line in her left antecubital fossa. On hospital day 16, the patient complained of worsening chest pain and had an elevated troponin of 2, but no signs of ischemia on EKG. Repeat echo was performed, which showed increase in size of the pericardial effusion and right ventricular collapse during diastole, concerning for impending tamponade (Figure 2).

Figure 2. Video of the transthoracic echocardiography showing a pericardial effusion (top arrow) with RV collapse during diastole (bottom arrow), concerning for impending cardiac tamponade.

The patient remained hemodynamically stable. Pericardial window was performed. 500 cc of purulent fluid was drained, and a pericardial drain was placed. Intra-operative fluid culture grew MSSA. The drain was left in place for 13 days. The patient was treated with a 4-week course of oxacillin. Blood cultures obtained on hospital day 28 were negative. A repeat echo was normal. The patient was discharged without further complications.

Discussion

Bacterial pericarditis is a rare, but fatal infection, with 100% mortality in untreated patients (1). After the introduction of antibiotics, the incidence of bacterial pericarditis declined to 1 in 18,000 hospitalized patients, from 1 in 254 (2). The most implicated organisms are Staphylococcus, Streptococcus, Hemophilus and M. tuberculosis (3).  Historically, pneumonia was the most common underlying infection leading to purulent pericarditis, especially in the pre-antibiotic era (2). Since the widespread use of antibiotics, purulent pericarditis has been linked to bacteremia, thoracic surgery, immunosuppression, and malignancy (3).

Acute pericarditis is a common complication in SLE with incidence of 11-54% (4), though few cases of bacterial pericarditis were reported in SLE patients. The organisms in these cases were staphylococcus aureus, Neisseria gonorrhea and mycobacterium tuberculosis (5). Despite these reports, acute pericarditis secondary to immune complex mediated inflammatory process remains a much more common cause of pericarditis than bacterial pericarditis in SLE (6). There’s minimal data to determine whether the incidence of bacterial pericarditis in patients with SLE is increased compared to the general population; however, there is a hypothetically increased risk for purulent pericarditis in SLE given the requirement for immunosuppression. Disease activity is yet another risk factor for bacterial infections in SLE, which is thought to be a sequalae of treatment with high doses of steroids (7). In this case, the patient had an SLE flare on presentation with SLEDAI-2K score of 13. Both immunosuppression and bacteremia may have precipitated this patient’s infection with bacterial pericarditis.   

Diagnosis of bacterial pericarditis requires high index of suspicion, as other etiologies of pericarditis are far more common. In this case, we initially attributed the patient’s pericarditis to her SLE flare. The patient’s fever on hospital day 15 prompted the infectious work up. MSSA pericarditis was diagnosed later after the pericardial fluid culture grew MSSA. Delay in the diagnosis can be detrimental as patients may progress rapidly to cardiac tamponade. 

Treatment requires surgical drainage for source control along with antibiotics (8). In our case, the patient required pericardial window and placement of a drain for 13 days. In bacterial pericarditis, the purulent fluid tends to re-accumulate; therefore, subxiphoid pericardiostomy and complete drainage is recommended (8). In some cases, intrapericardial thrombolysis therapy may be required if adhesions develop (8). With appropriate source control and antibiotics therapy, survival rate is up to 85% (8). 

Conclusion

Bacterial pericarditis is a rare infection in the antibiotic era, though some patients remain at risk for acquiring it. Despite the high mortality rate, patients can have good outcomes if bacterial pericarditis is recognized early and treated.

References

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Cite as: Anis A, Varda M, Dudar A, Schmitz ED. MSSA Pericarditis in a Patient with Systemic Lupus Erythematosus Flare. Southwest J Pulm Crit Care Sleep. 2022;24(2):32-35. doi: https://doi.org/10.13175/swjpccs057-21 PDF