Reviewed by EFIC on April 30, 2020
Headache medication and the COVID-19 pandemic
(Journal of Headache Pain, 25 April 2020)
Type of article: Commentary, brief literature analysis
Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)
Population: Patients suffering chronic headache and treated with ACE inhibitors (ACE-I), angiotensin II receptor blockers (ARB) or ibuprofen
Results: Concern has arisen in view of a putative link between the use of inhibitors of the renin-angiotensin system (ACE-I, ARB) and ibuprofen and an increased risk for COVID-19 infection. The authors discuss this concern in relation to headache treatment and conclude that, based on current evidence, there is no reason to abandon treatment with ACEI, ARB or ibuprofen in people with headache. There is no convincing evidence in medical / research literature that either renin-angiotensin system blockers or ibuprofen worsen SARS-CoV-2 infection in any type of patient, including headache patients.
Implications: The authors, in agreement with the advice of international cardiovascular societies, see no rationale to alter the prescription of these drugs that have an important role in the treatment of headache.
Commentary: There is no reason, empirical or scientific, to discontinue a treatment with ACE-I/ARB or ibuprofen in patients with COVID-19 infection. Discussion on mechanisms is short but sensible and rich. Conclusions are in line with recent results from Zhang et al (Circ. Res 2020, doi: 10.1161/CIRCRESAHA.120.317134.), that shows absence of complications and even better outcome in hypertensive patients with Covid19 treated with ACE-I/ARB.
Read the full article here.
Caring for patients with pain during the COVID‐19 pandemic: consensus recommendations from an international expert panel
(Anesthesia, 7 April 2020)
Type of study: Practice recommendations to help with the care of chronic pain patients during the COVID-19 pandemic.
Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles).
Results: Consensus recommendations on a range of topics including:
- face to face consultations (not recommended)
- telemedicine (recommended providing fits with legislative regulations)
- biopsychosocial management (recommended if social distancing can be maintained or using remote consultations)
- maintain regular review of patients prescribed opioids and that all patients receive their prescription of opioids to avoid withdrawal; and
- patients may continue prescribed NSAIDs for pain relief.
Commentary: The paper gives an overview of the expert opinion of a panel. However, the size of panel not stated. While the quality low, evidence in the paper may provide a benchmark for comparison to any local practice.
Read the full article here.
Characteristics, symptom management and outcomes of 101 patients with COVID-19 referred for hospital palliative care
(Journal of Pain and Symptom Management, April 2020)
Type of study: retrospective analysis of 101 medical and nursing case notes by clinician-researchers
Level of evidence: Level 4 (case series)
Results: Of the 101 patients with COVID-19 infection referred for end-of-life palliative care 64 were males and 37 females with a median age of 82 [72-89]. The most prevalent symptoms were in descendent order breathlessness, agitation, drowsiness, pain, and delirium. Apart from non-pharmacological treatment, patients received mainly symptom-relieving drugs with a median final dose of 10 mg/24 h morphine and 10 mg/24 h midazolam. Patients spent a median of 2 [1–4] days under the palliative care team and received 3 [2–5] contacts. 75 patients died, 13 were discharged and 13 remained under palliative inpatient care.
Implications: This retrospective analysis of a case series of COVID-19 patients receiving end-of-life palliative care instead of a referral to an intensive care ward gives some interesting insights into the course of the disease, the main symptoms under which the patients suffer, the required treatment measures, and their effectiveness.
Commentary: Intriguing is the information on end-of-life palliative care patients with COVID-19 infection in comparison to the intensive care patients that receive much more media attention. However, it provides little new information for the commonly known palliative care. The therapies that were initiated belong to the standard of care.
Read the full article here.
Pain Management Best Practices from Multispecialty Organizations during the COVID-19 Pandemic and Public Health Crises
(Pain Medicine, 7 April 2020)
Type of study: Narrative review
Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)
Results: This consensus provides a good overview on safety precautions to reduce risks of infection with SARS-CoV-2 for clinicians working in pain management and the patients they treat. Other issues considered include patient flow issues and staffing plans, telemedicine options, triaging recommendations and resource utilization, and impacts on mental health of both patients and healthcare workers. Guidance on the prescription of opioids and use of steroids for interventions is provided
Commentary: The paper summarises the opinions of an expert panel that included pain management experts from the military, Veterans Health Administration, and academia in the US. Hence, the recommendations reflect current practices in the US and may not be directly applicable in other settings.
Read the full article here.
Reviewed by EFIC on April 24, 2020
Acute use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19
(RPS NHS, 14 April 2020)
Type of study: Systematic review
Results: A systematic literature search identified 156 references but found no studies that determined whether acute use of non-steroidal anti-inflammatory drugs (NSAIDs) is related to increased risk of developing COVID-19 or increased risk of a more severe illness. Although NSAIDs may reduce acute symptoms of acute respiratory tract infection (such as fever), they may either have no effect on or worsen, long-term outcomes.
Implications: When people are starting treatment for fever and/or pain with confirmed or suspected COVID-19, all treatment options, including paracetamol and NSAIDs, should be considered and selected based on the greatest benefit compared to potential harms using each medicine.
Commentary: NSAIDs are common treatments for pain, fever, and inflammation. On 14th March 2020 possible concerns about their use in people with COVID-19 were raised due to an apparent observed worsening in the severity of symptoms in people taking anti-inflammatory medicines. There is currently no evidence that the acute use of NSAIDs causes an increased risk of developing COVID-19 or of developing a more severe COVID-19 disease.
The full article can be found here.
The role and response of palliative care and hospice services in epidemics and pandemics: a rapid review to inform practice during the COVID-19 pandemic
(Journal of Pain and Symptom Management, 8 April 2020)
Type of study: A rapid systematic literature review of published case studies, cross-sectional studies, cohort studies, and intervention studies
Level of evidence: Level 3A (Systematic review of case-control studies)
Results: Out of 2207 identified studies, 36 underwent full-text review, and 10 studies were finally selected for analysis.
To guide hospices and palliative care teams they should focus on:
- maintaining the ability to respond rapidly and flexibly;
- ensuring protocols for symptom management and psychological support, and non-specialists are trained in their use;
- being involved in triage;
- considering shifting resources from inpatient to community settings;
- considering redeploying volunteers to provide psychosocial care;
- facilitating camaraderie among staff and adopting measures to deal with stress;
- using technology to communicate with patients and carers; and
- adopting standardised data collection systems to inform operational changes and improve care.
Implications: Palliative care teams need to be flexible and rapidly redeploy resources in the face of changing needs during a pandemic, such as COVID-19. Particular attention should be to the triage of patients, palliative care expertise staff, workload and stress, anticipatory allocation of space and equipment, and standardised documentation of data.
Commentary: This rapid review provides guidance for hospices and palliative care teams to ensure that they do not become overwhelmed by rapid developments of a pandemic. There was limited detail about how studies were selected for undergoing full-text review. In addition, there was only limited evidence and a lack of quantitative data, no assessment of quality of studies, and no grading of recommendations. The use of a developed palliative care surge plan might have been used as a filter for the selection of studies. Despite these limitations, this paper gives a valuable review of literature relevant for palliative care and provides important guidance.
Read the full text here.
Cannabidiol as prophylaxis for SARS-CoV-2 and COVID-19? Unfounded claims versus potential risks of medications during the pandemic
(RSAP, 31 March 2020)
Type of study: Letter to the Editor
Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)
Results: During the COVID-19 pandemic, many patients may look for natural remedies to protect themselves. Use of products containing cannabinoids have proliferated amidst claims of health benefits including immune “support” or “boosting”. Cannabidiol (CBD) and tetrahydrocannabinol (THC) have complex pharmacological properties, including anti-inflammatory effects, that may be useful in certain conditions (including autoimmune and neurodegeneration diseases). However, they suppress cytokines, chemokines, effector T-cells, and microglial cells, reducing the host response to pathogens including viruses like SARS-CoV-2.
Implications: Current pharmacological and clinical evidence suggest CBD and THC decrease the body’s ability to fight infections, in particular viral and respiratory infections. In a clinical trial of cannabidiol for epilepsy, respiratory infections (pneumonia) were over 30% more common in those receiving CBD versus placebo. The author recommends avoiding the use of cannabinoids during this pandemic unless medically supported for recognised indications (e.g. seizures, cancer, chronic pain), and highlights false marketing claims of medical benefit including “immune system boosting” or antiviral effects, that should be reported to regulatory bodies.
Commentary: A very concise yet well-documented summary of the potentially serious problems of health-marketing as applied to cannabis. The analysis is USA-centred, where the direct advertisement and marketing of medicines is greater than in Europe.
Read the full article here.
Safety of ibuprofen in patients with COVID-19: causal or confounded?
(CHEST, 31 March 2020)
Type of article: Commentary
Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)
Results: This commentary retraces the origins of the worldwide alarm towards the use of ibuprofen, starting with a tweet from the French Health Minister who, after 4 young people reportedly developed serious COVID-19 disease after taking NSAIDs, advised that ibuprofen could aggravate the infection. The report, although unpublished, was reported in The BMJ and endorsed by specialists from France and UK, and by the WHO.
The authors criticise the low level of evidence of these reports, as well as the notion, published in The Lancet, that ibuprofen could enhance coronavirus infectivity by increasing the bioavailability of angiotensin converter enzyme (ACE), to which the virus binds. They argue that drawing conclusions from theoretical pharmacology is dangerous and can lead to erroneous results, such as the hypothesis that co-administration of ibuprofen and aspirin could counteract antiplatelet effectiveness, which was based on pharmacological thromboxane levels but then refuted in a randomized controlled trial.
Implications: Rather than concluding that ibuprofen is safe for COVID-19 related fever, the authors observe that current epidemiologic evidence “is not strong enough to infer a causal link of a harmful effect of ibuprofen in COVID-19”. They advise, however, that patients with COVID-19 take acetaminophen monotherapy for fever reduction.
Commentary: A very interesting critique of the multiple biases and insufficiencies that have polluted medical literature on this topic. It is, however, amusing that after such a clear analysis the authors end up recommending the same approach –paracetamol (acetaminophen) – as the French Minister in his initial tweet.
Read the article in full here.
Associations between immune-suppressive and stimulating drugs and novel COVID-19
(eCancer, 27 March 2020)
Type of study: Review
Level of evidence: 3A (systematic review of a variety of study types including in-vitro-, case-, in-vivo, animal- and human studies).
Results:
NSAIDs: The search did not identify any strong evidence for or against the use of ibuprofen for treatment of COVID-19 specifically.
Corticosteroids: Some evidence that corticosteroids may be beneficial in the treatment of SARS-CoV. However, this is not specific to COVID-19.
Commentary: There is no definitive evidence that NSAIDs or corticosteroids are contraindicated in COVID-19.
Read the full article here.
Latest EMA advice on the use of non- steroidal anti-inflammatories for COVID-19
(DTB, March 2020)
The European Medicine Agency has issued advice on the use of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in people who are infected with the Coronavirus disease (COVID-19).
The published article states that there is currently no scientific evidence establishing a link between ibuprofen and the worsening of COVID-19. It advises that when treating fever or pain in people with covid19, patients and healthcare professionals should take into account the harms and benefits of all available treatment options including paracetamol and NSAIDs.
People who have been advised to use ibuprofen by a healthcare professional should therefore not stop taking it. EMA is monitoring the situation closely and will review any new information that becomes available on this issue in the context of the pandemic and EFIC will make sure to keep everyone updated by making the news available on our website.
Read and download the full article here.