2 Minute Medicine Rewind November 2, 2020

Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia

1. There is no difference in overcorrection rate when using slow continuous infusion or rapid intermittent bolus administration of hypertonic saline to correct hyponatremia.

2. Use of a rapid intermittent bolus strategy is associated with a lower incidence of requiring relowering therapy and with an increased incidence of achieving target correction rate within one hour.

Evidence Rating Level: 1 (Excellent)

The most common electrolyte imbalance encountered in clinical practice, hyponatremia, is often treated with hypertonic saline. Both under- and over-correction, however, are associated with toxicity. Correction with small, fixed boluses is recommended by recent guidelines due to perceived efficacy, safety, and ease of administration. There is a paucity of data, however, clarifying whether hypertonic saline is best administered via slow continuous infusion (SCI) or by rapid intermittent bolus (RIB). This randomized controlled trial compared 87 patients managed with RIB (mean [SD] age = 72.9 [12.4] years, 48.3% male) with 91 patients managed with SCI (mean [SD] age = 73.2 [12.1] years, 41.8% male). The primary outcome was the incidence of overcorrection of hyponatremia. Mean serum sodium in both the RIB and SCI cohorts was 118.2 mmol/L. It was found that overcorrection occurred in 15 patients in the RIB cohort and 22 patients in the SCI cohort (absolute risk difference -6.9, 95% CI -18.8 to 4.9, p = 0.26). The RIB cohort, however, showed a lower incidence of requiring relowering treatment than the SCI cohort (41.4% vs. 57.1%, absolute risk difference -15.8%, 95% CI -30.3% to -1.3%, p = .04). This translates to a number needed to treat of 6.3. Furthermore, patients in the RIB cohort, on average, reached target correction rate within one hour more frequently than did patients in the SCI cohort (32.2% vs. 17.6%, absolute risk difference 14.6%, 95% CI 2% to 27.2%, p = 0.02) This translates to a number needed to treat of 6.8. In all, this study showed that correction of hyponatremia with both RBI and SCI is safe and effective with no difference in overcorrection rate, though RBI may be the preferred strategy due to a lower incidence of requiring relowering therapy and higher incidence of achieving target correction rate within one hour.


Discontinuing Nasal Continuous Positive Airway Pressure in Infants ≤32 Weeks Gestational Age: A Randomized Control Trial

1. Among infants born ≤ 32 weeks gestational age requiring nasal continuous positive airway pressure (NCPAP), a gradual pressure wean to 3 cm H2O versus stopping at the level of approximately 5 cm H2O did not change the total number of days spent on NCPAP.

Evidence Level Rating: 1 (Excellent)

For infants born prematurely, nasal continuous positive airway pressure (NCPAP) is a mainstay of respiratory support that decreases the need for mechanical ventilation, improves outcomes, and minimizes the incidence of bronchopulmonary dysplasia. It is not, however, without risks; NCPAP is associated with an increased risk of nasal septal injury, pneumothorax, and gastric distention, among others. As such, there is a desire to minimize time spent on NCPAP. This randomized controlled trial examined two strategies of stopping NCPAP – gradual pressure weaning to 3 cm H2O (wean cohort) and stopping at the level of approximately 5 cm H2O (control cohort) – among premature infants ≤ 32 weeks gestational age. The primary outcome was the total days of NCPAP, defined as the need for any NCPAP support within a 24-hour period. 116 infants were randomized to the control cohort (mean [SD] age = 28 [2] weeks, 55% male) and 110 infants to the wean cohort (mean [SD] age = 29 [2] weeks, 51% male). It was found that the total number of days on NCPAP did not differ significantly between the control and wean cohorts (median 16 vs. 14 days, p = 0.56). However, the control cohort was nearly twice as likely to fail the first attempt at stopping NCPCP (p = 0.01) and four-times more likely to have two or more failed attempts at stopping (p < 0.01). In a subgroup analysis, grouping infants 23 to 27 and 28 to 32 weeks gestational age, there was again no difference in the primary outcome. Overall, this study demonstrated that stopping NCPAP at 5 cm H2O compared with a gradual pressure wean from 5 to 3 cm H2O had no difference on the total duration of NCPAP therapy among infants ≤ 32 weeks gestational age, though a strategy of gradually weaning pressure significantly decreased the incidence of failure to stop NCPAP.


Ultrasound Examination of the Lymphatic Drainage Area and Regional Lymph Nodes in Melanoma Patients with In-Transit Metastases

1. Among patients with cutaneous melanoma, ultrasound evaluation identified in half of patients in-transit metastases that were otherwise not apparent during clinical examination and changed the course of management for a third of patients.

Evidence Leve Rating: 3 (Average)

In-transit metastases (ITMs), or lesions that develop in lymphatics between the primary tumor site and the regional lymph node field, occur in about 4% of patients with cutaneous melanoma. ITMs carry serious prognostic implications; approximately 43% of patients will go on to develop lethal, distant metastases. Thus, reliable ways of identifying ITMs are important for the management of patients with melanoma. This case series from an Australian institution evaluated the impact of using high-frequency ultrasound examination in patients with melanoma and ITMs, specifically looking at the incidence of additional ITMs, the false-positive rate, and the impact on management. 28 patients (median [IQR] age = 72 [63-77] years, 57% male) with a total of 40 ITMs were studied. Ultrasound examination identified additional ITMs in 54% of patients compared with clinical examination alone. Most of these additional ITMs were closer to the regional lymph node field than clinically apparent ITMs. The sensitivity and specificity of detecting additional metastases was 78% and 90%, respectively, with only one false-positive node confirmed after excision. Of note, a previous study found the sensitivity and specificity of PET/CT, a radiation-based imaging modality, for staging patients with ITMs to be 58% and 83%, respectively. Importantly, in 32% of patients, subsequent medical or surgical management was influenced by ultrasound evaluation. In all, this study suggests that ultrasound is a useful staging modality for patients with cutaneous melanoma as it both sensitive and specific for ITMs and has the potential to affect the course of management.


Quality of Outpatient Depression Treatment in Patients With Comorbid Substance Use Disorder

1. Patients with co-occurring substance use disorder and depression were less likely to received guideline-concordant treatment for depression, both in terms of pharmacology and psychotherapy, when compared with patients with depression alone.

Evidence Level Rating: 2 (Good)

It is not uncommon to find depression and substance use disorders (SUD) co-occurring, and the combination of the two leads to poorer outcomes. As such, treatment of depression is a priority for patients with SUD. However, to date there is no data examining whether patients with co-occurring SUD and depression receive similar care to those without SUD for both pharmacological- and psychotherapy-based treatment modalities. This retrospective cohort study involved veterans receiving care through the U.S. Veterans Health Administration, including 53,034 patients diagnosed with a new episode of depression, of whom 28,081 received antidepressant treatment and 18,484 received psychotherapy. In this particular cohort, 7,516 patients had a diagnosed SUD in the year prior to their diagnosis of depression. It was found that, despite having more contact with the health care system on average, patients with SUD received less guideline-concordant depression treatment across all metrics. Indeed, with regards to pharmacotherapy, acute- and continuous-phase antidepressant treatment was provided to 59.4% and 36.3%, respectively, of patients with co-occurring depression and SUD. In contrast, 66.2% and 44.8% of patients without SUD received acute- and continuous-phase antidepressant treatment. This same pattern was observed among patients receiving psychotherapy; 31.6% and 26.8% of those with SUD received acute and continuation phases of depression treatment, respectively, compared with 35.4% and 32.2% of those without SUD. Furthermore, it was found that among specific SUDs, patients with alcohol, opioid, and cannabis use disorders were more likely to receive lower-quality depression care in the acute phase. In all, this study involving a large cohort from the nation’s largest provider of health care indicates a treatment gap among those with co-occurring SUD and depression. More research needs to be done to identify strategies to deploy more equitable and effective treatment plans for patients with both SUD and depression.


Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial

1. In a small cohort of patients, IL-2 elevation after gluten challenge appears to be the earliest and most sensitive marker of gluten exposure and may play a role in non-invasive diagnostics of celiac disease in the future.

Evidence Level Rating: 2 (Good)

Celiac disease (CeD), an immune-mediated disorder, has an estimated prevalence of approximately 0.7% and is associated with diarrhea, abdominal pain, malabsorption, infertility, and malignancy, among others. Diagnosis of CeD is currently based on a combination of patient-reported symptoms, serological biomarkers, and histological damage seen in mucosal biopsies, all of which have their limitations. This double-blind, randomized controlled trial evaluated the effects of gluten exposure on serum levels of specific biomarkers that may have diagnostic utility. Patients with biopsy-proven CeD in remission were randomized 1:1 to received either 3 g gluten/day or 10 g gluten/day for 14 days. The primary study outcome was villous height to crypt depth ratio (Vh:Cd) at 15 days. 7 patients receiving 3 g gluten and 7 receiving 10 g gluten underwent endoscopic biopsy after gluten challenge. At 15 days, there was a significant change in Vh:Cd in the 10 g cohort (p = 0.0025), while a non-significant change was seen in the 3 g cohort (p = 0.23). All patients had an increased intraepithelial lymphocyte (IEL) count (p = 0.0078). Other dose- and time-dependent changes were noted in the two cohorts. On day 15, there was a 1.5-fold increase of CD8+ T cells in the 3 g cohort and a 1.6-fold increase in the 10 g cohort. In particular, patients in the 10 g cohort were shown to have a 27.1-fold increase in proliferating (Ki67+) memory CD8+ T cells in the epithelium. IL-2 levels also increased in 12 of 14 patients just four hours after gluten challenge (p = 0.0008). After accounting for multiple comparisons, the relationship between IL-2 and IEL count was significant (r = 0.83, p = 0.0004, false discovery rate = 0.018), suggesting its utility in diagnosis. Although the sample size of this study was quite small, it did show how a serum biomarker like IL-2 could feasibly be used in the clinic to assist in the diagnosis of CeD, providing the potential for less invasive investigation.

Image: PD

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