Landiolol- Game Changer in Management Atrial Fibrillation ICU Patients ( Sepsis)

Landiolol is an ultra-short-acting, highly cardioselective β1-blocker developed primarily in Japan and increasingly studied worldwide for rapid rate control in atrial fibrillation (AF), especially in acute care settings.

Key Pharmacologic Properties:

• Half-life: ~4 minutes, enabling rapid titration and withdrawal.

• β1/β2 selectivity: ~255:1 (far higher than esmolol), minimizing bronchospasm and vasodilation.

• Onset: Within minutes.

• Clearance: Independent of hepatic or renal function.

Clinical Benefits:

• Effective rate control in AF (especially postoperative, ICU, or hemodynamically unstable patients).

• Minimal negative inotropic effect, making it safer in patients with impaired LV function compared to other beta-blockers.

• Less hypotension than esmolol or diltiazem due to high β1 selectivity and absence of β2-mediated vasodilation.

• Rapid titration allows tight control of HR without prolonged hemodynamic compromise.

Dosing:

• Initiate without a bolus: e.g., 1–10 mcg/kg/min, titrate every 10–15 minutes.

• Max doses vary by indication but typically up to 40 mcg/kg/min.

• No loading dose is necessary, unlike esmolol.

Use in Sepsis and Critical Illness:

• In septic patients with persistent tachycardia after adequate fluid resuscitation, landiolol has been studied for:

  • Reducing heart rate

  • Preserving or improving cardiac output

  • Avoiding hypotension seen with other beta-blockers

• J-Land Study (2013) and subsequent European studies have shown:

  • Safe HR control in septic shock with no increased risk of hypotension or organ dysfunction

  • Improved diastolic filling, reduced myocardial oxygen demand, and possible anti-inflammatory effects

  • No benefit on controlling persistent sinus tachycardia in sepsis- more recent studies

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Clinical Considerations:

• Ideal for ICU patients with AF, particularly in postoperative cardiac surgery, sepsis, or HF with reduced ejection fraction.

• Caution in patients with severe bradycardia, AV block, or profound shock.

• Offers advantages over amiodarone (slower onset, QT prolongation, poor rate control) and diltiazem (vasodilation, hypotension).

• When transitioning to oral beta-blockers:

  1. Administer the oral beta-blocker

  2. Ten minutes later, reduce the landiolol infusion rate by 50%

  3. If satisfactory control is maintained for at least one hour, discontinue landiolol

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Summary Statement:

Landiolol is an ultra-short-acting, β1-selective IV beta-blocker that provides rapid, titratable rate control in atrial fibrillation with minimal risk of hypotension or negative inotropy. Its excellent hemodynamic profile makes it suitable for use in critically ill patients, including those with sepsis and persistent tachycardia, where conventional beta-blockers may be poorly tolerated.

Shock Index

Explaining shock index (SI)

Shock index (SI) is the ratio of heart rate (HR) to systolic blood pressure (SBP), expressed in beats per minute over mmHg. A normal resting SI is about 0.5 to 0.7 in healthy adults. When there's hypovolemia or shock, SI increases, providing an earlier warning than HR or SBP alone. It helps in risk stratification for conditions like trauma, sepsis, or MI. Thresholds above 0.7 signal abnormality, and values over 1.3 suggest high risk or need for interventions. However, it's limited in certain conditions like beta-blockade or hypertension.

Shock Index (SI) = heart rate ÷ systolic blood pressure
 e.g. 110 beats min⁻¹ ÷ 100 mm Hg = 1.10 (unit‑less)

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Why it matters physiologically

When circulating volume falls or systemic vascular tone drops, the body tries to maintain cardiac output by raising heart rate while SBP drifts downward. The ratio changes earlier than either vital sign alone, so SI flags occult shock before frank hypotension appears. 

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What the number tells you

Range (adult)	Typical interpretation	Clinical evidence/examples
0.5 – 0.7	Normal resting SI in healthy adults	—
> 0.7	Early hemodynamic stress; prompts closer monitoring	Predicts need for intervention in ED sepsis cohort.
≥ 0.9	Abnormal—high likelihood of compensated shock	Used as escalation trigger in obstetric hemorrhage guidelines.
≥ 1.0	Decompensation imminent; higher ICU admission & mortality	Linked to massive‑transfusion requirement after trauma.
≥ 1.4–1.7	Severe shock; urgent resuscitation needed	Strong predictor of adverse outcome in postpartum hemorrhage and septic shock meta‑analyses.

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Key clinical uses

• Trauma & hemorrhage – SI > 0.9 at arrival identifies patients who will need massive transfusion or operative control even when vital signs look “normal.” 

• Sepsis – Persistently elevated SI after fluids correlates with progression to septic shock, vasopressor requirement, and increased 28‑day mortality. 

• Post‑partum hemorrhage – Obstetric protocols use SI ≥ 0.9 for transfer/activation and ≥ 1.3–1.7 for calling massive‑bleed teams. 

• Myocardial infarction, pulmonary embolism, stroke – SI adds prognostic discrimination over SBP or HR alone. 

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Practical points & limitations

• Trend it. A rising SI is often more informative than any single value.

• Age or pediatric adjustment. In children SI normally runs higher; the SIPA score uses age‑specific cut‑offs. 

• Confounders. β‑blockers, pacemakers, atrial fibrillation, high spinal cord injury, or severe pain/anxiety can mask or exaggerate SI.

• Derived variants. Modified SI (HR ÷ MAP), Delta‑SI (arrival vs. prehospital), and Age‑SI (SI × age) may improve accuracy in specific settings but are not yet widely adopted.

Take‑home: Shock index is a quick bedside metric that integrates heart rate and systolic blood pressure into a single early‑warning number—values ≥ 0.9 signal compensated or overt shock and should trigger an immediate search for bleeding, sepsis, cardiogenic failure, or other causes, plus aggressive resuscitation and monitoring.

Explaining Sepsis Reassessment

What the chart auditors are looking for

Under the CMS SEP‑1 six‑hour bundle, any patient who is still hypotensive after the 30 mL kg‑¹ bolus or whose initial lactate is ≥ 4 mmol L‑¹ must have a “repeat volume‑status and tissue‑perfusion assessment” completed and documented by an LIP before the 6‑hour clock runs out. If that note is missing or incomplete, the entire case fails the measure. 

Auditors often key on boiler‑plate phrases such as “Sepsis reassessment completed”—but the note must also satisfy one of the three documentation pathways below.

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1. Focused exam (the classic five‑bullet exam)

A single attestation that the LIP performed a repeat focused exam after the fluid bolus and documented all five of these items:

1. Vital signs

2. Cardiopulmonary exam

3. Capillary‑refill time

4. Peripheral‑pulses assessment

5. Skin findings

If any of the five bullets is missing, the element fails.

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2. Review of ≥ 5 of the 8 CMS‑listed parameters

Instead of a physical exam, the LIP may state that they reviewed at least five of the following eight data points:

• Vital signs

• Cardiopulmonary assessment

• Capillary‑refill

• Peripheral pulses

• Skin colour/condition

• Arterial O₂ saturation

• Urine output

• Shock index (HR/SBP)

Example text that passes:

“Sepsis reassessment completed 14:12. Reviewed VS, cardiopulmonary exam, cap‑refill < 2 s, peripheral pulses 2+, skin warm, UO 45 mL h‑¹.” 

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3. Any 2 of 4 hemodynamic tests

The LIP may instead document that they obtained or interpreted two of these:

• Central‑venous pressure (CVP)

• Central‑venous oxygen saturation (ScvO₂)

• Bedside cardiovascular ultrasound (IVC or LV filling)

• Dynamic fluid‑responsiveness test (passive‑leg‑raise or 250‑mL fluid challenge)

Example:

“Reassessment 15:05 – CVP 10 mm Hg; PLR ↑ stroke volume 16 %. No further fluid indicated.” 

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Practical documentation tips

Tip	Why it helps
Use an EHR smart phrase such as “.sepsisreassessment” that auto-populates all five bullets or prompts you to pick the 8‑parameter route.	Prevents missing elements.
Time‑stamp the note after the bolus but before 6 h.	Auditors match it to the bundle clock.
If nurses collect pulses or urine output, the LIP must explicitly state they reviewed those RN findings.	RN data alone doesn’t count.

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Bottom line:
“Sepsis reassessment completed” only meets SEP‑1 when the note shows either the five‑bullet focused exam, or review of ≥ 5 of CMS’s eight surrogate parameters, or two hemodynamic tests—documented by an LIP and time‑stamped within the 6‑hour window. Anything less will be marked non‑compliant.

Thoracentesis in Acute Decompensated Heart Failure

 Clinical Perspective

What Is New?

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TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion–Interventional Trial) is the first randomized controlled trial to investigate the effectiveness of upfront therapeutic thoracentesis in addition to standard medical therapy compared with medical therapy alone in patients admitted to the hospital with acute heart failure and pleural effusion.

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A strategy of referring to upfront therapeutic thoracentesis did not increase the number of days alive out of the hospital over the following 90 days, survival probability, or patient-reported quality of life, and did not reduce the duration of the index admission.

What Are the Clinical Implications?

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In patients with acute heart failure, left ventricular ejection fraction ≤45%, and sizable pleural effusion (amenable for thoracentesis but less than two-thirds of the hemithorax), reducing filling pressures with diuretics and guideline-directed medical therapy should be the primary treatment target, because the addition of therapeutic thoracentesis does not contribute to a shorter duration of admission or a more favorable prognosis in the following 90 days.

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Routine referral to upfront therapeutic thoracentesis is not recommended, but can be considered on an individual basis after carefully considering potential complications.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073521

direct link to PDF in Paperpile

Common Causes of Altered Mental Status in Elderly patients

 The most common causes of altered mental status in elderly patients include:

1. Infections: Urinary tract infections, pneumonia, and sepsis are frequent culprits[1][2][3]. Even COVID-19 can cause altered mental status in older adults[5].

2. Metabolic disturbances: Electrolyte imbalances, dehydration, and organ dysfunction (e.g., hepatic encephalopathy) can lead to mental status changes[2][3][6].

3. Medications and drugs: Polypharmacy, drug interactions, overdose, or withdrawal from substances like benzodiazepines and opioids can cause altered mental status[1][2][3].

4. Neurological conditions: Stroke, brain hemorrhage, brain tumors, and seizures can affect mental status[2][3][5].

5. Delirium: This is a common presentation of altered mental status in the elderly, occurring in 7%-10% of geriatric patients in the emergency department[8]. It can be caused by various underlying factors, including those mentioned above.

6. Chronic conditions: Dementia, Parkinson's disease, and other neurodegenerative disorders can contribute to altered mental status[1][5].

7. Toxin exposure: Exposure to substances like carbon monoxide or cyanide can affect mental status[5].

8. Metabolic disorders: Thyroid imbalances and vitamin deficiencies can lead to altered mental function[3].

It's important to note that in elderly patients, the cause of altered mental status is often multifactorial, with several contributing factors present simultaneously[1][2].

Citations:

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC3614410/

[2] https://www.aafp.org/pubs/afp/issues/2021/1100/p461.html

[3] https://www.webmd.com/mental-health/what-is-altered-mental-status

[4] https://hign.org/consultgeri/resources/symptoms/abrupt-change-mental-status

[5] https://www.mayoclinic.org/diseases-conditions/delirium/symptoms-causes/syc-20371386

[6] https://my.clevelandclinic.org/health/diseases/23159-altered-mental-status-ams

[7] https://www.hmpgloballearningnetwork.com/site/emsworld/article/10850982/acute-altered-mental-status-elderly-patients

[8] https://reference.medscape.com/slideshow/altered-mental-status-elderly-6010546

Pulmonary artery pressures by echocardiography

 Measurement of pulmonary artery pressure and  grading by echocardiography with emphasis on new guidelines  

1. Estimation method:

The pulmonary artery systolic pressure (PASP) is typically estimated using the peak tricuspid regurgitation velocity (TRV) and adding an estimate of right atrial pressure[1][2]. This is done using the simplified Bernoulli equation: PASP = 4(TRV)^2 + estimated right atrial pressure.

2. Grading scale:

The severity of pulmonary hypertension based on mean pulmonary artery pressure (mPAP) is generally graded as[4]:

- Mild: 20-40 mmHg

- Moderate: 41-55 mmHg

- Severe: > 55 mmHg

3. Probability assessment:

Recent guidelines recommend assessing the probability of pulmonary hypertension rather than providing a specific pressure estimate[1][3]. The echocardiographic probability of pulmonary hypertension is categorized as:

- Low probability: TRV ≤ 2.8 m/s or not measurable, with no other echocardiographic signs of PH

- Intermediate probability: TRV ≤ 2.8 m/s with other signs of PH, or TRV 2.9-3.4 m/s without other signs

- High probability: TRV 2.9-3.4 m/s with other signs of PH, or TRV > 3.4 m/s

4. Additional echocardiographic signs:

Other echocardiographic parameters are considered when assessing the probability of pulmonary hypertension, including right ventricular size and function, pulmonary artery characteristics, and inferior vena cava and right atrium measurements[1][3].

5. Limitations:

It's important to note that numerical echocardiographic estimates of pulmonary artery pressure often are inaccurate compared to invasive measurements, with both overestimation and underestimation possible[1][2]. Right heart catheterization remains the gold standard for diagnosing pulmonary hypertension[4].

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In summary, while specific pressure values can be estimated, current guidelines emphasize assessing the probability of pulmonary hypertension using a combination of tricuspid regurgitation velocity and other echocardiographic signs, rather than relying solely on pressure estimates.

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Citations:

[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6055509/

[2] https://www.ccjm.org/content/83/4/256

[3] https://echo.biomedcentral.com/articles/10.1530/ERP-17-0071

[4] https://litfl.com/pulmonary-hypertension-echocardiography/

[5] https://www.sciencedirect.com/science/article/abs/pii/S2213260021000722

[6] https://www.ahajournals.org/doi/10.1161/jaha.113.000363

[7] https://www.ahajournals.org/doi/10.1161/circimaging.116.005711

Xylazine Adulteration of the Heroin–Fentanyl Drug Supply: A Narrative Review" published in Annals of Internal Medicine, 2023

Introduction:

- The article provides a comprehensive review of the increasing prevalence of xylazine (a non-opioid sedative and analgesic often used in veterinary medicine) as an adulterant in the illicit heroin and fentanyl supply.

- Emphasis on the public health implications, the pharmacology and toxicology of xylazine, and the challenges it poses in the context of the current opioid epidemic.

Background:

- Xylazine, primarily used in veterinary practice for sedation, muscle relaxation, and analgesia, has been increasingly identified in the illegal drug market, particularly combined with opioids such as heroin and fentanyl.

- Its non-controlled status in many areas contributes to its rise as a common adulterant, offering a cheaper alternative for drug augmentation.

Pharmacology of Xylazine:

- Acts as an α2-adrenergic agonist, inducing sedative, muscle relaxant, and analgesic effects; it does not produce the same euphoric effects as opioids.

- In humans, xylazine can cause significant central nervous system depression, bradycardia, hypotension, and respiratory depression, which are exacerbated when combined with opioids.

- The sedative effects of xylazine contribute to its abuse potential, particularly when combined with the euphoric effects of opioids.

Public Health Implications:

- The addition of xylazine increases the risk of overdose and death, particularly as users may be unaware of the adulterant and its potent effects on respiratory depression.

- It complicates treatment for overdose; naloxone, an opioid antagonist used to reverse opioid overdose, does not counteract xylazine's effects, making resuscitation more challenging.

- The presence of xylazine can significantly strain emergency medical services and harm reduction efforts due to the increased complexity and severity of overdoses.

Epidemiological Concerns:

- Geographical variations in xylazine prevalence in the drug supply, with certain areas seeing a significant increase in xylazine-related incidents and others remaining relatively unaffected.

- An upward trend in xylazine adulteration, suggesting its establishment as a common component in the illicit drug market, possibly due to its accessibility and potentiation of opioid effects.

Challenges and Future Directions:

- Limited awareness and lack of routine testing for xylazine in many toxicology screenings for drug overdose, resulting in underreporting and mischaracterization of overdose incidents.

- Need for increased surveillance and research to fully understand the scope of xylazine's impact on the opioid epidemic and to inform public health and policy responses.

- Urgent call for integrating xylazine awareness into harm reduction strategies, enhancing healthcare provider education, and updating protocols for overdose response.

- Importance of policy-making efforts addressing the regulation of xylazine, improving access to treatment for substance use disorders, and enhancing the strategies for managing drug supply adulteration.

Conclusion:

- The adulteration of the heroin–fentanyl supply with xylazine poses a significant and growing public health challenge.

- Coordinated efforts involving public health policy, improved medical response, targeted research, and community-based harm reduction strategies are essential in addressing the complications introduced by xylazine in the ongoing opioid crisis.