[Combination diuretic therapy in heart failure]. / Combinaties van diuretica bij hartfalen.

Loop diuretics are the cornerstone of the treatment of volume overload in decompensated heart failure. However, often complete decongestion cannot be achieved rapidly with loop diuretics alone, partly due to compensatory upregulation of sodium resorption at other parts of the nephron. These compensatory mechanisms can be antagonized by using a combination of diuretics. In earlier research, a number of those combinations have been investigated, but no diuretic combination has been proven to be both efficient and safe yet. A recent multicenter, double-blind, randomized, placebo-controlled study - performed by Mullens et al. in 2022 - investigated adding acetazolamide (Diamox) to loop diuretics in patients with decompensated heart failure. They found that a higher rate of decongestion was achieved with the addition of acetazolamide without seemingly more side effects. The addition of acetazolamide can be considered in the treatment of decompensated heart failure.

[Toxidromes]. / Toxidromen.

In this Clinical Lesson, using two illustrating cases, we explain how to do the initial assessment and treatment of an intoxicated patient. An approach aimed at toxidromes can serve as a stepping stone. A toxidrome is a combination of symptoms and clinical features that can occur with the use of certain drugs and substances. The most commonly encountered toxidromes are sympathomimetic, serotonergic, anticholinergic, cholinergic, sedative-hypnotic and opioid. All patients need to be approach according to the ABCDE method. The treatment is based on pharmacokinetics by means of the ADME principle (absorption, distribution, metabolism and excretion) and based on pharmacodynamics, aimed at the toxidrome.

[Consider (es)ketamine for treatment-resistant depression]. / Overweeg (es)ketamine bij therapieresistente depressie.

Major depressive disorder has a high prevalence globally. Although pharmacotherapy and psychotherapy are effective for most patients, about one third is treatment resistant. Ketamine, known as an anesthetic, is a new treatment option that can be effective in patients with treatment-resistant depression. (es)ketamine works relatively fast. However, the long-term effects are still relatively unknown. In the Netherlands, S-Ketamine is currently administered in various forms, of which only the nasal spray is registered for treatment-resistant depression. Currently, many studies have been conducted on the use of (es)ketamine. In this article we describe the latest state of affairs regarding its effectiveness and safety.

[Dealing with opioid dependence and withdrawal in hospitals]. / Omgaan met opioïdafhankelijkheid en -onthouding in het ziekenhuis.

BACKGROUND: In opioid addiction tolerance occurs requiring substitution with unusually high doses. A balance must be struck between the risk of overdose with respiratory depression and QTc interval prolongation on one hand and underdosing with withdrawal syndrome on the other hand. An unreliable anamnesis can complicate adequate dosing. CASE DESCRIPTION: A 30-year-old polydrug user with a severe dependence on methadone and heroin was admitted to the Intensive Care Unit after surgery for thoracic surgery. Upon cautious initiation with methadone, severe withdrawal and pain symptoms occurred. Doubling the dose made the withdrawal symptoms disappear without signs of overdose. CONCLUSION: During hospital admission of patients with high opioid tolerance the anamnestic equivalent high opioid dose can be started immediately, provided there is a possibility of monitoring the respiration and heart rhythm. The risk of withdrawal and insufficient pain relief in a hospital is generally greater than the risk of an overdose.

[Topical NSAIDs: ineffective or undervalued?] / Topicale NSAID's: ineffectief of ondergewaardeerd?

Topical NSAIDs are currently recommended in several national and international guidelines for knee osteoarthritis, hand osteoarthritis and acute musculoskeletal pain. However, there is still widespread skepticism about the effectiveness of this treatment. This article discusses different reasons for this skepticism, a short summary of the pharmacokinetics and pharmacodynamics of topical NSAIDs and an overview of available evidence regarding efficacy and safety. Based on this evidence topical NSAIDs have a clear place in the treatment of knee and hand osteoarthritis and acute musculoskeletal pain. Due to less systemic side effects they should be recommended before an oral NSAID is considered. Topical NSAIDs might even be an option for patients with contra-indications for oral NSAIDs. There is a large variety of available topical NSAIDs. Of the available topical NSAIDs in the Netherlands, diclofenac gel seems the most sensible choice.

[Black particles in plasma and carcinogenic pills]. / Zwarte deeltjes in plasma en kankerverwekkende pillen.

Recently in a national newspaper presumed large hazards in care were described. Visible black particles were seen in blood plasma and a cancerogenic substance was found in paracetamol. Every year 300.000 bags of plasma are produced. The black particles were found in 11 bags of plasma. Possibly one of these was administered. During administration 175 micron filters are used. Presumably remaining particles will be degraded by the mononuclear-phagocytic system. In paracetamol 6 ppm of para-chloroaniline was found. Depending of the limit used by either the ICH or the EFSA this means for patients using lifelong 6 grams of paracetamol a risk off respectively 1: 200.000 or 1:20.000. This risk is neglectable compared of the life time risks of cancer in the population (1:3). Journalists should realize that this exaggerated commentary can lead to real serious risks (taking NSAID's instead of paracetamol) and mistrust in regular care.

[Medication during severe infections]. / Medicatiegebruik bij patiënten met ernstige infecties.

Severe infectious diseases result in an increased volume of distribution. Renal function is usually impaired, but can in fact be increased early in the course of the disease. In renally cleared drugs with a small therapeutic index a dose reduction should take place or these medications should be temporarily discontinued. Renally cleared antibiotics may be subject to subtherapeutic levels of antibiotics, especially early in the course of the disease. Diuretics and RAAS inhibitors should usually be interrupted during acute illness; bèta-blockers should be continued. Statins can usually be continued. Paracetamol can usually be prescribed. NSAIDs, however, are almost always contra-indicated. Patients with chronic use of corticosteroids should receive a stress dose. There is no evidence to support discontinuing immunosuppressants. Platelet aggregation inhibitors and directly acting oral anticoagulants are continued, whereas coumarins should be monitored vigorously or substituted for low molecular weight heparins.