CRIT CLOUD - Summaries & Reviews

No Need to Withhold Preoperative Antibiotic Prophylaxis

Fri, 02 Jan 2026 22:50:58 GMT

Patients undergoing removal or replacement of an infected hip joint prosthesis routinely have intraoperative cultures taken to identify the causative pathogen and guide targeted antimicrobial therapy. A longstanding concern has been that administering standard preoperative antibiotic prophylaxis might compromise bacterial detection or reduce the sensitivity of these cultures.

Fortunately, the available evidence is clear and reassuring: standard preoperative antibiotic prophylaxis — including cefuroxime — should not be withheld in this setting.

The most recent consensus from the American Academy of Orthopaedic Surgeons supports the routine administration of prophylactic antibiotics prior to hip replacement surgery, even when infection is present. The key points are as follows:

Withholding preoperative antibiotics is associated with an increased risk of additional surgical site infections.
Randomized controlled trials and cohort studies consistently demonstrate that preoperative antibiotic prophylaxis does not significantly reduce the sensitivity or positivity rate of intraoperative cultures, particularly when modern microbiological techniques are employed.
There is no evidence to suggest that withholding prophylactic antibiotics improves the diagnostic accuracy of intraoperative cultures.

In summary, current evidence strongly supports the continued use of standard preoperative antibiotic prophylaxis in patients undergoing surgery for infected hip prostheses. This approach optimizes patient safety without compromising microbiological diagnostics — a clear win for both infection control and clinical decision-making.

Diagnosis and Prevention of Periprosthetic Joint Infections: Evidence-Based Clinical Practice Guideline. American Academy of Orthopaedic Surgeons (2019).

The Effect of Preoperative Antimicrobial Prophylaxis on Intraoperative Culture Results in Patients With a Suspected or Confirmed Prosthetic Joint Infection: A Systematic Review. Wouthuyzen-Bakker M, Benito N, Soriano A. Journal of Clinical Microbiology. 2017;55(9):2765-2774. doi:10.1128/JCM.00640-17.

Periprosthetic Joint Infection. Patel R. The New England Journal of Medicine. 2023;388(3):251-262. doi:10.1056/NEJMra2203477.

Preoperative Antibiotic Prophylaxis in Prosthetic Joint Infections: Not a Concern for Intraoperative Cultures. Pérez-Prieto D, Portillo ME, Puig-Verdié L, et al. Diagnostic Microbiology and Infectious Disease. 2016;86(4):442-445. doi:10.1016/j.diagmicrobio.2016.09.014.

Should we Remove Calcium from our Resus Trolleys?

Tue, 02 Dec 2025 08:46:52 GMT

It was the paradigm par excellence, the first emergency measure for hyperkalaemia with ECG changes or arrhythmias: the administration of calcium gluconate.

However, this recently published, large systematic review changes everything. And it was already obvious before, but no one simply looked closely enough:

“There was no evidence to support a clinical beneficial effect of calcium for treatment of hyperkalaemia.”

This review examined 101 studies published up to 2024 to determine which pharmacological drugs are truly effective in acute hyperkalaemia. Two of these studies examined this in patients with cardiac arrest.

The result of this work was sobering and clear. Neither calcium gluconate nor bicarbonate resulted in a relevant reduction in potassium levels. It is repeatedly stated that calcium stabilises membranes, based on studies from the 1960s. However, even the presumed “membrane stabilisation” does not seem to be truly verifiable.

Calcium gluconate did not improve hyperkalaemia-related ECG changes and even had a worse outcome in the context of resuscitation!

Calcium-Gluconate

There is NO clinical benefit of calcium in the treatment of hyperkalaemia
There is NO evidence of an improvement in ECG changes
Calcium gluconate during resuscitation was even associated with a worse outcome

Bicarbonate

There is NO evidence of any clinically relevant benefit of bicarbonate
Bicarbonate has NO effect on potassium levels

Insulin-Glucose-Infusion

Insulin and glucose are effective in treating hyperkalaemia, with an average reduction in potassium of 0.7–1.2 mmol/L.

Beta-Agonists (Salbutamol/Albuterol)

Inhaled administration lowers potassium levels by an average of 0.9 mmol/L
Intravenous administration of salbutamol with insulin lowers potassium most efficiently (by an average of 1.2 mmol/L)

NEW ILCOR-Guidelines 2025 on the Treatment of Hyperkalaemia

Intravenous Insulin and Glucose, Beta-Agonists or the combination of both are clearly recommended.

Routine use of Sodium-Bicarbonate is NOT recommended (very low evidence).
No clear Recommendation for Calcium-Gluconate (very low evidence)
For the usage of Calcium-Gluconate during cardiac arrest there is simply insufficient evidence and the possibility of harm

Read the article: Review Article - ILCOR 2025

Everything about COX-Inhibitors - Formerly known as NSAID's

Tue, 03 Jun 2025 08:51:35 GMT

When it comes to commonly used painkillers, there are so many different types and categories that it can be quite tricky to get a clear overview. But did you actually realise?

All commonly used painkillers work by the same way: Inhibition of Cyclooxygenase - or short COX!

This isn’t just true for the well-known non-steroidal anti-inflammatory drugs (NSAIDs), but also for medications like metamizole and paracetamol. So, the term “NSAIDs” is actually outdated and misleading — COX-inhibitors would be a much more accurate way to describe them as a common group of medications! The term “non-steroidal analgesics” also suggests that steroids are analgesics — which is not correct either!

Cyclooxygenase inhibitors (COX inhibitors) are medications that reduce inflammation, alleviate pain, and lower fever. They are widely used in conditions such as arthritis, injuries, infections, and other inflammatory diseases.

The way these drugs influence COX though is different and therefore is their mode of action.

COX 1 is continuously produced by many tissues and helps protect the stomach lining, maintain kidney function and regulate blood clotting through platelets

COX 2 is inactive under normal conditions but is produced during inflammation. COX 2 generates Prostaglandines that intensify pain and promote swelling and fever.

There are 3 kinds of COX inhibitors:

Non-Selective COX inhibitors: (e.g. ibuprofen and naproxen) inhibit both COX 1 and COX2. They are effective but can irritate the gastrointestinal tract.

Selective COX-2 inhibitors: (e.g. etoricoxib, celecoxib) primarily inhibit COX-2 and are designed to avoid stomach-related side effects.

Central COX inhibitors: Other agents like paracetamol and metamizole act through central COX inhibition and are safer for many patients but lack anti-inflammatory properties.

All COX inhibitors offer pain and fever reduction. However, anti-inflammatory effects are only seen with COX-2 inhibition. Platelet inhibition, important for cardiovascular protection, is achieved through COX-1 inhibition (e.g., aspirin).

The selective inhibition of COX-2 alone is sufficient to achieve maximum analgesic and anti-inflammatory effects.

Recognising the fact that COX-2 inhibition is sufficient for therapeutic effects, while COX-1 inhibition causes many side effects, led to the development of selective COX-2 inhibitors - so called Coxibs.
Although COX-2 selectivity is beneficial, concurrent COX-1 inhibition (e.g., with aspirin) may reduce cardiovascular risk. Selectivity is based on a small structural difference between COX-1 and COX-2 (isoleucine vs. valine at position 523).

All Coxibs inhibit COX-2 in the central nervous system as well.

Benefits of Coxibs:

Fewer COX-1-related side effects
Reduced GI complications
Fewer bronchial allergic reactions (e.g., salicylate asthma, Samter’s triad)
No increased bleeding risk
Potential advantages in specific cases (e.g., inflammatory bowel disease outside of acute flares) compared to non-selective COX inhibitors.

Even with all their advantages, COX-2 inhibitors (Coxibs) haven’t completely taken over the NSAID world—and there are some good reasons:

Coxibs are a valuable option—especially for patients at high GI risk—but they haven’t replaced non-selective NSAIDs because of:

- Cardiovascular safety concerns! Increased risk for heart attacks and strokes.
- Higher cost. Often more expensive and less widely available.
- Some traditional NSAIDs (like indometacin or naproxen) are still preferred in specific indications (e.g. acute gout, pericarditis) due to their stronger COX-1 activity or longer half-life.
- Physician caution based on past experience, these drugs still have no long term records.

Let's have a closer look at the most common COX-inhibitors used.

Diclofenac

Diclofenac is a fast-acting, potent non-selective COX inhibitor with slight COX-2 preference (non-selective) and serves as a reference drug for comparing other COX inhibitors. It achieves maximum analgesia through COX-2 inhibition, penetrates inflamed tissue and the CNS well, and has enhanced tissue targeting due to its acidic pKa and plasma protein binding.

However, its clinical use is limited by variable absorption, a short half-life (2–4 h), and gastrointestinal and hepatic side effects. High dosing (e.g., 2×75 mg/day) is common but may cause unnecessary adverse effects, including GI erosion and rare severe hepatotoxicity.
In general, erosions of the gastric mucosa can be expected after just a few days of use. Protective measures such as proton pump inhibitors or misoprostol cannot prevent direct damage to the mucosal lining. Hepatotoxicity or nephrotoxicity caused by diclofenac is independent of gastric protection.

Ibuprofen

Ibuprofen, an arylpropionic acid derivative and preferential COX-1 inhibitor (non-selective), is generally well tolerated, especially at low doses (200–400 mg). At standard daily doses (600–1200 mg), it causes fewer GI side effects than high-dose diclofenac, but at high doses (3×800 mg), its side effect profile (GI and cardiovascular risks) is similar to diclofenac or etoricoxib.

Due to short half-life requires three daily doses
It does impair kidney function and is not recommended in renal insufficiency.
Importantly, ibuprofen interferes with the cardioprotective effect of low-dose aspirin (ASS) if taken simultaneously — proper timing is essential. If taken three times daily, aspirin’s effect is fully blocked.

Indometacin

Indometacin is a potent COX-1 inhibitor (non-selective) with good penetration into inflamed tissue and the nervous system. It is mainly used for ankylosing spondylitis, acute gout attacks, and prevention of heterotopic ossification. In obstetrics, it is used to close a patent ductus arteriosus in newborns. Its use is limited by frequent GI and central nervous system side effects, such as headache and dizziness.

Ketolorac

Ketorolac, a preferential COX-1 inhibitor (non-selective) is often used as eye drops, but in many countries, it is an important intravenous alternative to morphine for treating postoperative pain. It relieves pain up to six hours and is generally well tolerated. There is an association though with a risk of GI-bleeding and renal failure.

By the way: It is an isomer of ibuprofen and structurally related to indometacin.

Naproxen

Naproxen, also a preferential COX-1 inhibitor (non-selective), is widely used in the U.S. but less so in Europe. Due to its long half-life (12–15 hours) and strong COX-1 affinity, it significantly inhibits platelet aggregation, increasing the risk of gastrointestinal bleeding and interactions with anticoagulants. However, this effect also contributes to its lower cardiovascular risk compared to other COX inhibitors.

Acetylsalicylic Acid - Aspirin

Aspirin holds a unique position among COX inhibitors. Developed by Felix Hoffmann, the acetylation of salicylic acid improved its tolerability and broadened its effects. At low doses (50–100 mg/day), aspirin irreversibly inhibits COX-1in platelets, preventing aggregation and offering cardioprotection. This effect persists for several days due to the lack of nucleus in platelets.
At higher doses (2–3 g/day), aspirin also inhibits COX-2, producing anti-inflammatory and analgesic effects, but significantly increases gastrointestinal side effects due to its acidic nature (pKa 3.0).
Notably, aspirin also inhibits NFκB, iNOS, and COX-2 expression—effects that go beyond enzymatic COX inhibition.
Pharmacokinetically, the irreversible COX inhibition means aspirin’s duration of action is not tied to plasma levels. The half-life of salicylic acid increases with dose due to enzyme saturation.

Indications:

Cardiovascular prevention at low doses (50–100 mg/day)
High-dose use (2–3 g/day) for inflammation or pain (e.g., rheumatic disease), though this increases side effects
Emergency treatment for heart attack or stroke via IV aspirin-lysine
Topical salicylic acid is used for keratolysis (e.g., corns)

325 mg tablets, common in the U.S., are considered unnecessarily high for cardiovascular prevention.

Paracetamol

Paracetamol (acetaminophen) is widely used as a first-choice analgesic and antipyretic for mild to moderate pain, especially in children, pregnant women, and the elderly, due to its low side-effect profile.
Did you know: The IV form (Perfalgan®)offers the most effective analgesia!

Despite recurring concerns about safety, especially in high doses or misuse, paracetamol remains one of the safest options when used correctly--no COX inhibitor matches its safety at equal analgesic doses.

Mechanism of Action:

Inhibits COX-2 and PGE2 synthesis in the nervous system.
Its metabolite AM404 prolongs endocannabinoid activity by preventing reuptake of anandamide, modestly boosting analgesia.

Paracetamol has NO Anti-inflammatory Effect!
Though it inhibits COX-2, paracetamol has no anti-inflammatory effect. This is because it can’t reduce the high peroxide levels in inflammatory cells needed to block PGH2 synthesis effectively.

Metamizole

Metamizole (also known as dipyrone) is a potent analgesic, antipyretic, and spasmolytic drug used for severe pain, including tumor pain, high fever, and biliary or urinary colic. It's a prodrug and rapidly converted to 4-MAA, a reversible, non-selective COX-1/COX-2 inhibitor with central nervous activity.
Its COX inhibition is comparable to diclofenac or ibuprofen and likely explains its strong analgesic effect. However, it does not reduce inflammation, and unlike other COX inhibitors. Metamizole:

Does not impair platelet aggregation
Does not harm the gastric mucosa
Does not significantly affect kidney function

This lack of typical COX-inhibitor side effects may be due to biochemical antagonism of anti-inflammatory pathways.
At high doses, metamizole opens potassium channels and reduces calcium influx in smooth muscles, relieving colic pain but also contributing to blood pressure drops. Despite its clinical usefulness, long-term safety data is limited, especially regarding rare but serious side effects like agranulocytosis.

Conclusion

Mild pain and fever: Paracetamol or ibuprofen are good first-line options.
Inflammatory pain: Diclofenac or etoricoxib are more effective.
Severe or colicky pain: Metamizole is a strong option, especially in hospitals.
Fever in children: Paracetamol is preferred due to safety.
Heart and stroke prevention: Low-dose aspirin is used for its anti-platelet effects.

Want to get more insight into this topic, read this excellent article on COX-inhibitors (Original in German):

Hemmstoffe_der_Cyclooxygenase.pdf
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Current Treatment Options for COVID 19 - In a Nutshell!

Tue, 12 Jan 2021 20:33:48 GMT

The treatment and management options of COVID-19 patient are rapidly evolving. The amount of research published daily is endless so that keeping an overview seems almost impossible.

This short review of current publications is intended to overview current treatment options and its evidence. We will look at:

- How do you Identify and Triage Patients at Risk for Severe Disease?

- What about High Flow Nasal Cannulas (HFNC) and Non-Invasive Ventilation (NIV)?

- Should we Prone Position the Spontaneously Breathing Patient?

- When to Use Corticosteroids?

- Should we Use Remdesivir?

- What about Convalescent Plasma?

- How do we Manage Thromboprophylaxis?

How do you Identify and Triage Patients at Risk for Severe Disease?

In an ideal world, we would be able to assess newly admitted patients with COVID-19 to predict the risk of getting critically ill in the course of the disease. Apart from a proper clinical assessment, JAMA published the COVID-GRAM Risk Score to address this problem.

They used a cohort of 1590 patients to develop this score and validated this with a cohort of 710 patients. From 72 potential predictors, ten variables were independent predictive factors and were included in the risk score.

The practicability in a clinical setting is not clear yet, and as any predictive score, there are several limitations when it comes to assessing a single patient instead of a cohort.

The COVID-GRAM Score Calculator can be accessed via the following link: http://118.126.104.170/

Early identification of COVID-19 patients at risk for severe disease would be helpful for management. Every clinic/ ICU should have a triage and risk assessment tool at hand.

For triage, we use the following simple criteria:

As a predictive assessment tool for severe disease
the COVID-GRAM Calculator can be used:

COVID-GRAM Calculator:
http://118.126.104.170/

Liang W et al. JAMA Intern Med. 2020;180(8):1081-1089.

What about High Flow Nasal Cannulas (HFNC) and Non-Invasive Ventilation (NIV)?

Especially at the beginning during the first wave of the pandemic, the use of HFNC and NIV was often avoided due to aerosolisation fear. Many ICU's tended to intubate their patients with respiratory failure relatively early.

The lack of ventilators in some areas and reports that invasive ventilation is associated with high mortality (Zhou F, Lancet 2020; 395:1054) led to a constant change in management.

KEEP IN MIND: Randomised-controlled studies for the treatment of COVID-19 patients with HFNC and NIV lack until now!

Aerosolisation remains a big concern for health care workers (Niedermann MS; Am J Respir Crit Care Med 2020; 201:1019, Wu Z; JAMA 2020, February 24) and the amount of leakage flows is highly variable (Winck JC; Pulmonology 2020, April 20).

Experience during the year 2020 showed, that most critical care providers have moved to use NIV and HFNC more frequently than initially. Proper personal protection equipment is essential and minimises risk for health care providers. Some evidence supports this approach (Avdeev SN, Am J Em Med AJEM Volume 39, p 154-157).

NIV and HFNC is feasible in patients with COVID-19 and acute hypoxemic respiratory failure, even outside the ICU

Helmet-NIV, leakage-free masks (non-vented masks) and double hose systems with virus-proof filters seem to be advantageous in this respect
(Pfeiffer M; Pneumologie 2020, April 22).

It is recommended that patients under HFNC should wear a surgical face mask over their cannulas

Helmet NIV might advantageous compared to Mask NIV, though evidence is limited.
(Patel BK et al. JAMA 2016. PMID: 27179847, single center study, trial stopped early, larger randomized-controlled studies awaited).

KEEP IN MIND: Generally, there is only minimal evidence regarding the therapeutic benefit of these measures compared to their risks for the environment due to aerosolisation.

Whether HFNC and NIV itself might produce self-inflicted lung injury (SILI) to some extend is not fully understood!

Following patients should be considered for intubation and invasive ventilation

- Severe hypoxemia (PaO2/FiO2 <150mmHg or respiratory rate >30/min)
- Persistent or worsening respiratory failure (i.e. O2 sat <88%, RR > 36/min)
- Neurologic deterioration
- Intolerance of face mask or helmet
- Airway bleeding
- Copious respiratory secretions

Should we Prone Position the Spontaneously Breathing Patient?

Since the publication of Guerin C et al. (N Engl J Med 2013; 368:2159) prone positioning of patients with moderate to severe ARDS has become standard procedure in ICU's around the world. It is, therefore, evident that this treatment modality seems appropriate for COVID-19-induced lung injury, too.

Trying to avoid intubations, clinicians rose the question, whether a prone position in the spontaneous breathing patient could avoid the need for invasive ventilation or even improve outcome.

Ding L et al. (Crit Care 2020; 24:289) published a small multicenter study including 20 patients, whereas in 11 patients intubation could be avoided by prone positioning patients under NIV or HFNC.

Telias et al. published an JAMA editorial (JAMA. 2020;323(22):2265-2267). He states that the prone position can improve oxygenation and can potentially result in less injurious ventilation. Unfortunately, this does not necessarily equate to lung protection and a better outcome. While improved oxygenation might prevent clinicians from intubating a patient, delayed intubation might worsen the patient's outcome.

Regarding some evidence showing improved oxygenation during prone position, there are reasons to give it a try (Caputo ND et al. Acad Emerg Med Published online April 22, 2020).

In the hypoxemic patient with no relevant respiratory distress awake prone positioning is a valid option

- Use nasal cannulas or HFNC first
- If comfortable enough, ask the patient to self-prone
- Encourage the patient to remain in the prone position as long as well tolerated
- Patients need close nursing and appropriate monitoring
- Select prone positioning mattresses might be of help

When to Use Corticosteroids

Patients with COVID-19 often show a biphasic course of the disease. The first phase is characterised by profound virus replication which decreases significantly after 5-7 days. After 7-10 days, a second phase develops in which an excessive or dysfunctional immune response can appear. This can lead to ARDS and multi-organ failure, which might be tackled by immunomodulating therapy.

The largest, pragmatic randomised control trial we have at this stage is RECOVERY, performed in 176 hospitals around the UK and including more than 6400 patients (RECOVERY Collaborative group, N Engl J Med, July 17, 2020). COVID-19 patients that required oxygen or mechanical ventilation and presented with symptoms for at least seven days showed a significant reduction in 28-day mortality when treated with 6 mg Dexamethason OD for up to 10 days. Patients in the early viremic phase or patients that not required any oxygen performed worse with Dexamethasone.

A broader insight into this topic brings a meta-analysis from JAMA in September 2020, including seven studies: DEXA-COVID19, CoDEX, RECOVERY, CAPE COVID, COVID STEROID, REMAP-CAP and Steroids-SARI. They ended up looking at 1703 patients and found a significant reduction in 28-day mortality when treated with steroids compared to placebo.

Patients with COVID 19 that require oxygen, HFNC, NIV, mechanical ventilation or ECMO should be treated with steroids

In patients not requiring oxygen, there is a trend towards harm when giving steroids - In these situations, steroids are NOT indicated

Should we Use Remdesivir?

Brief: Evidence in regards to the treatment with remdesivir is scattered and inconclusive.

In the largest randomised control triad available so far is ACTT-1 looking at about 1600 patients (Beigel JH et al. N Engl J Med 2020; 383:1813-1826). In a few words, remdesivir showed a trend towards a 4-5 day shorter time to recovery, but not if symptoms existed for more than nine days. There was no significant influence on mortality, except maybe for patients requiring oxygen but not any help in ventilation. If at all, remdesivir might provide some advantage in a very selected patient group, but even this remains debatable. For this reason, many consider remdesivir the 'Tamiflu for COVID-19'.

Two other papers remain to be mentioned briefly:

Wang et al. (The Lancet; April 29) presented results from a relatively small study which was terminated early and showed no statistically significant clinical benefits of remdesivir - except for a trend towards a shorter duration of illness.

Goldmann JD et al. presented the so-called '5 versus 10 days study', a phase 3 multicentre study with 397 patients. The primary outcome was their clinical status on day 14, secondary outcome patients with adverse events. Interestingly a 5-day course of remdesivir resulted in a better clinical outcome that a 10-day course. Again, It did not show any benefit compared to placebo.

Remdesivir - The "Tamiflu for COVID-19"

There is insufficient evidence to recommend the use of Remdesivir strongly. It is expensive, and if used, maybe there is only a short time window reasonable to act.

Should We Use ECMO?

During the early phase of the pandemic, first reports raised some concern that ECMO in COVID-19 patients might be associated with very high mortality (Henry BM et al. J Crit Care; 58:27). In the meanwhile, though we have new results from a more extensive cohort study looking at data from the Extracorporeal Life Support Organisation (ELSO, Barbaro RP et al. Lancet Volume 396, ISSUE 10257)

The investigators looked at 1035 COVID-19 patients from 36 countries that were treated with ECMO (mean age 49 years, 74% male). 70% of all patients had relevant co-morbidities. The median time of ECMO support was 14 days. The incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4%. Mortality was 39% in patients with a final disposition of death or hospital discharge.

These results are comparable with earlier mult-centre studies with patients suffering from non-COVID-19 ARDS (Combes A et al. N Engl J Med 2018; 378:1965).

A retrospective cohort study from France looking at 83 patients treated with ECMO showed a probability to die after 60 days of 31%. Mortality at the time of the last follow-up was 36% (Schmidt et al. Lancet Respir Med 2020; 8:1121-1131).

Various Societies recommend the use of ECMO in COVID-19 patients with treatment-refractory lung failure (Surviving Sepsis Campaign, ESICM, SCCCM and ELSO, WHO)

Regarding the ongoing pandemic and limited resources, uniform indication and selection criteria for ECMO use should be available

What about Convalescent Plasma?

After a negative small randomised control trial (Li L et al. JAMA. 2020;324(5):460-470), a controversial Emergency Use Authorisation was granted by the FDA on 23.8.20 due to an observational study with a favourable effect on mortality with a high specific IgG content and onset less than days after symptom onset (Joyner MJ et al. MedRxiv; https://doi.org/10.1101/2020.08.12.20169359 - non peer-reviewed).

At this stage the use of covalescent plasma can not be recommended

How do we Manage Thromboprophylaxis?

COVID 19 undoubtedly causes an inflammatory state that seems to trigger thrombotic activation in the venous and the arterial circulation. Thromboembolic complications are common, but the evidence is not robust on whether prophylactic or therapeutic doses should be used.
Patients often have a significant elevation of D-dimers, an acute phase reactant representing the severity of disease rather than the dosage of thromboprophylaxis.

One observational study looking at 1716 patients found no improved outcomes among in-hospital patients with COVID-19 when treated with therapeutic anticoagulation compared to prophylactic dosing. Moreover, patients who were started on anticoagulation for COVID-19 without evidence of thrombosis, new VTE, or new atrial fibrillation had worse outcomes compared to patients who were on prophylactic anticoagulation (Patel NG et al. Thrombosis Update; Volume 2 , 2021, 100027)

A case-based review of current literature and the COVID-19 specific coagulopathy end with the same finding that all in-hospital patients should receive prophylactic thromboprophylaxis. Whether a higher dose of prophylactic anticoagulation may be more effective is currently unknown (Chen EC et al. Oncologist . 2020 Oct; 25(10): e1500–e1508.).

A small and retrospective study with 152 patients showed a lower risk of death and a lower cumulative incidence of thromboembolic events in patients with respiratory failure when a high-dose thromboprophylaxis was used. (Jonmarker S et al. Critical Care volume 24, Article number: 653 (2020)).

Evidence supports the use of prophylactic thromboprophylaxis in patients with COVID-19

Whether a higher dose of anticoagulation might be more effective is currently unknown

Made Easy - Nomenclature of Monoclonal Antibodies

Fri, 08 Jan 2021 09:43:44 GMT

This single slide turn you into an expert in the nomenclature of monoclonal antibodies, but also helps to understand quickly what sort of medication your patient is treated with. Share and Care!

Mind the GAPS Study - Compression Stockings are Useless for Most Elective Surgery Patients!

Mon, 14 Sep 2020 11:56:54 GMT

Cricoid pressure prevents aspirations, preoperative antibiotics avoid infections, and compression stockings protect against deep vein thrombosis. Many medical measures aim to reduce morbidity and mortality among patients, but unfortunately, the benefit of these measures is often not, or insufficiently, proven. Under certain circumstances, they may lead to additional problems or even cause harm (e.g. cricoid pressure Read Here).

Time has definitely come to take a closer look at compression stockings for surgical patients. Apart from the fact that they look terrible, they are just as uncomfortable to wear and even carry certain risks in patients with peripheral vascular disease, for example. The effectiveness of compression stockings in modern practice has been questioned, but robust evidence has been lacking.

This seems to change, as the long-awaited GAPS-Trial has been published and now provides further evidence on what concern patients undergoing elective surgery.

Among this population, adding compression stockings to pharmaco-thromboprophylaxis was non-superior compared to pharmaco-thromboprophylaxis alone (primary outcome). There was also no difference in the quality of life outcomes found (secondary outcome).

There is now some robust evidence to omit compression stockings in surgical patients that receive pharmacological thromboprophylaxis.

Shalhou J. et al. BMJ 2020;369:m1309

Antibiotics - Again Less Seems More - This Time: Uncomplicated Diverticulitis

Thu, 03 Sep 2020 07:50:09 GMT

The W.H.O. has repeatedly warned that antibiotic resistance is one of the biggest threats to global health today. Among all measures we can take to try and reduce this problem, merely avoiding unnecessary treatments is maybe one of the most effective.

It is therefore pleasing that another piece of good evidence has been published, supporting the avoidance of antibiotics in the event of non-complicated diverticulitis (defined as non-perforated diverticulitis with a Hinchey 1a grade in computed tomography).

The investigators performed a

randomized, placebo-controlled, double-blind trial

in which they compared 180 patients with non-complicated diverticulitis

to receive

either cefuroxime, metronidazole, and amoxicillin/clavulanic acid or placebo.

They found

No significant difference in the median time of hospital stay (primary outcome). Also, there were no significant differences between groups in adverse events, readmission to the hospital within one week, and readmission to the hospital within 30 days.

These findings complement other studies indicating that observational treatment without antibiotics can be considered appropriate in patients with uncomplicated diverticulitis.

Clin Gastroenterol Hepatol. 2020 Mar 30;S1542-3565(20)30426-2

More literature

Daniels L et al. BJS: https://doi.org/10.1002/bjs.10309

Int J Colorectal Dis. 2015 Sep;30(9):1229-34.

ARDS in COVID-19: Is it Time to Let Go of the High-PEEP Strategy?

Tue, 31 Mar 2020 16:07:23 GMT

The lastest updated surviving sepsis guidelines for COVID-19 patient recommends a high-peep strategy in the intubated, mechanically ventilated patient. As most of these patients present with moderate to severe ARDS, PEEP is used to keep lung areas open and therefor to improve oxygenation. This seems to be especially true in the classical case of ARDS, where the lung become 'wet' and 'heavy' which results in widespread atelectasis of the dependent parts of the lungs, often further complicated by pleural effusions.

Classical CT appearance in the acute phase of ARDS is an opacification with an antero-posterior density gradient. Dense consolidation in the most dependent regions merges into a background of widespread ground-glass attenuation and the normal or hyperexpanded lung in the non-dependent areas (Howling SJ et al. Clin Radiol 1998;53(2):105-109). The theory behind these changes is that the increased weight of overlying lung causes compression-atelectasis posteriorly. The fact that prone positioning these patients quickly redistributes these gradients supports this theory (Desai SR et al. Anaesthesiology 1991;74(1):15-23).

Classical ARDS finding in pneumococcal pneumonia

Chest CT's in patients with COVID-19 often show ground-glass opacification with or without consolidations. These are changes often seen in viral pneumonia. Several case series suggest, that CT abnormalities seem to be mostly bilateral and tend to have a peripheral distribution, often involving the lower lobes. In contrast to the classical ARDS pleural thickening, pleural effusion and lymphadenopathy seem to be a less common finding (Shi H et al. Lancet Infect Dis 2020).

ARDS in COVID-19 patient

The leading problem in COVID-19 patients with ARDS is hypoxemia, while hypercapnia does not seem to be a significant problem. Sometimes profound hypoxemia does not seem to correlate with patient symptoms at all. In regards to the images above, atelectasis might not be the predominant reason for V/Q mismatches in these patients.

Observations of mechanically ventilated patients in our unit and other hospitals in Switzerland have shown, that higher PEEP levels (15cmH2O and higher) often result in significantly reduced compliance values complicating ventilation and favouring the development of pulmonary over-inflation. This observation might support the theory that patients with COVID do not represent the traditional manner of ARDS with distinctive atelectasis. Another observation that supports this theory is that COVID-19 patients often do not respond as clearly to Prone Positioning as classical ARDS patients do.

More probably, V/Q mismatch seems so happen on a more microscopical level in COVID-Patients. Lung compliance is often normal on these patients and, therefore, applying high PEEP-levels does NOT add any benefit at all.

Maybe the principle of less is more also applies to COVID-19 patients we treat (Gattinoni L et al. Intensive Care Medicine; 46, pages780–782(2020))

Looking at the New Surviving Sepsis Campain COVID-19 Guidelines:
Given these considerations, the strategy with High PEEP-levels in general should be questioned in principle.

Surviving Sepsis Campaign COVID-19 Guidelines - Short Summary

Sun, 22 Mar 2020 00:45:32 GMT

The European Society of Intensive Care Medicine ESICM and the Society of Critical Care Medicine SCCM have been very efficient in providing us health care workers with a guideline manuscript giving recommendations on the treatment of COVID-19 patients in a critical care setting. It is imperative to keep in mind that research is moving forward very quickly in these times and changes to these recommendations are likely to occur.

A collection of many reliable OPEN ACCESS platforms on SARS-CoV-2 can be found on www.foam.education.

Infection Control

When performing aerosol-generating procedures on patients with COVID-19 in the ICU, fitted respirator masks (N95 respirators, FFP2) should be used (in combination with full Personal Protective Equipement PPE)

Aerosol-generating procedures on ICU patients with COVID-19 should be performed in a negative pressure room

During usual care for non-ventilated and non-aerosol-generating procedures on mechanically ventilated (closed circuit) patients surgical masks are adequate

For endotracheal intubation video-guided laryngoscopy should be used, if available

In intubated and mechanically ventilated patients, endotracheal aspirates should be used for diagnostic testing

Supportive Care

In COVID-19 patients with shock, dynamic parameters like skin temperature, capillary refilling time, and/or serum lactate measurement should be used in order to assess fluid responsiveness

For the acute resuscitation of adults with COVID-19, a conservative over a liberal fluid strategy is recommended

For the acute resuscitation of adults cristalloids should be used - avoid colloids!

Buffered/balanced crystalloids should be used over unbalanced crystalloids

Do NOT use hydroxyethyl starches!

Do NOT use gelatins!

Do NOT use dextrans!

Avoid the routine use of albumin for initial resuscitation!

In shock use norepinephrine/ noradrenaline as the first-line vasoactive agent

The use of dopamine is NOT recommended

Add vasopressin, if target MAP cannot be reached

Titrate vasoactive agents to target a MAP of 60-65 mmHg, rather than higher MAP targets

For patients in shock and with evidence of cardiac dysfunction and persistent hypoperfusion despite fluid resuscitation and norepinephrine, adding dobutamine should be used

For persistent shock despite all these measures, low-dose corticosteroids should be tried

Ventilatory Support

Keep peripheral saturation SpO2 above 90% with supplemental oxygen

There is NO need for supplemental oxygen with SpO2 above 96%

In acute hypoxemic respiratory failure despite conventional oxygen therapy, high-flow nasal cannulas (HFNC or High-Flow) should be used next

High-Flow should be used over non-invasive ventilation (NIV)

If High-Flow is not available and there is no urgent need for endotracheal intubation, NIV with close monitoring can be tried

In the event of worsening respiratory status, early endotracheal intubation should be performed

In mechanically ventilated patients, low-tidal volume ventilation should be used: 4 to 8 ml/kg

In mechanically ventilated patients with ARDS targeting plateau pressures (Pplat) of < 30 cm H2O should be aimed for

In patients with moderate to severe ARDS, a high-PEEP strategy should be used (PEEP >10cmH2O). Patients have to be monitored for potential barotrauma

NOTE by Crit.Cloud:

The strategy for high PEEP levels in general is currently discussed controversially. Observations in our own unit showed, that high PEEP levels tend to impaire compliance and therefor the quality of ventilation. Read also: "Less is More" in mechanical ventilatio, Gattinoni L. et al. Intensive Care Med (2020) 46:780-782

Patients with ARDS should receive a conservative/restrictive fluid strategy

In moderate to severe ARDS, prone positioning for 12-16 hours is recommended

To facilitate lung protective ventilation in moderate to severe ARDS, intermittent boluses of neuromuscular blocking agents (NMBA) should be used first

In the event of persistent ventilator dyssynchrony, the need for ongoing deep sedation, prone ventilation, or persistently high plateau pressures, a continuous NMBA infusion for up to 48 hours should be used next

Do NOT use inhaled nitric oxide in COVID-19 patients with ARDS routinely

In severe ARDS and hypoxemia despite optimising ventilation and other rescue strategies, a trial of inhaled pulmonary vasodilator as a rescue therapy can be considered; if no rapid improvement in oxygenation is observed, the treatment should be tapered off

If hypoxemia persists despite optimising ventilation, recruitment manoeuvres should be applied

If recruitment manoeuvres are used, DO NOT use staircase (incremental PEEP) recruitment manoeuvres

If all these measures fail, the patient should be considered for venovenous ECMO

COVID-19 Therapy

In mechanically ventilated patients WITHOUT ARDS, systemic corticosteroids should NOT be used routinely

In contrast, mechanically ventilated patients WITH ARDS, the use of systemic corticosteroids is recommended

Mechanically ventilated patients with respiratory failure should be treated with empiric antimicrobials/antibacterial agents

Critically ill patients with fever should be treated with paracetamol (acetominophen) for temperature control

In critically ill patients standard intravenous immunoglobulins (IVIG) should NOT be used routinely

Also, the routine use of convalescent plasma is NOT recommended

The routine use of lopinavir/ritonavir (Kaletra®) is NOT recommended

Currently, there is insufficient evidence to issue a recommendation on the use of other antiviral agents in critically ill adults with COVID-19

Currently, there is insufficient evidence to issue a recommendation on the use of recombinant interferons (rIFNs); chloroquine or hydroxychloroquine; tocilizumab (humanised immunoglobulin)

Direct Download of the pdf file:

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) by ESICM and SCCM

Safe Airway Management in COVID-19 Adult Patients

Fri, 20 Mar 2020 01:25:58 GMT

The Aerosol-Danger of SARS-Cov-2

The outbreak of the SARS Coronavirus-2 (SARS-CoV-2) in China 2019 has within a short time spread around the globe and is just about to hit central Europe. Although about 80% of all confirmed cases develop a mild febrile illness, around 17% develop severe Corona viral disease (COVID-19) with findings of acute respiratory distress syndrome (ARDS), of which about 4% will require mechanical ventilation.

Since this virus, which was previously unknown to humans, spread rapidly around the globe, a large number of patients requiring intensive medical care now arise within a very short time.

The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme ACE2, which is most abundant in type II alveolar cells of the lungs. This results in mainly type 1 respiratory failure, which often requires urgent tracheal intubation and mechanical ventilation.

Due to viral shedding in the patient's lungs, COVID-19 spread mainly via droplets. Events like coughing, high flow nasal oxygen (High-Flow), intubation and more can cause aerosol generation, allowing these airborne particles to travel even further distances.

Performing endotracheal intubation in these patients is, therefore, a high-risk procedure, and it is required to adhere to certain principles to avoid infection of health care providers.

The Safe Airway Societies of Australia and New Zealand have published a consensus statement that describes the problem very well and provides practical tips based on the currently available evidence.

1. Non Invasive Ventilation (NIV) and High Flow Nasal Oxygen (High-Flow)

Current evidence suggests that the failure rate of NIV in COVID-19 patients seems to be similarly high as observed among Influenza A patients. Failure in these patients resulted in higher mortality.

In general, NIV is recommended to be avoided or at least used very cautiously!

The utility of High-Flow in viral pandemics in unknown. There is some evidence suggesting a decreased need for tracheal intubation compared to conventional oxygen therapy.

High Flow Nasal Oxygen is worth a try, although it has to be assumed, that this is aerosol-generating.

High-Flow should only be used in (negative pressure) airborne isolation rooms, and staff should wear full personal protective equipment (PPE) including N95/P2 masks.

NIV and High-Flow are NOT recommended for patients with severe respiratory failure or when it seems clear that invasive ventilation is inevitable!

Full Personal Protective Equipment PPE

2. Environment for Airway Management

Negative pressure ventilation rooms with an antechamber are ideal. If not available, normal pressure rooms with closed doors are recommended. Positive pressure ventilation areas like in theatre should be avoided!

3. Intubation-Specific Recommendations

Use disposable equipment if possible

Prior to intubation oxygen can be delivered via nasal cannulas (standard or High-Flow), simple face-mask or non-rebreather mask.

NIV should be used very cautiously or be avoided due to its unproven utility in ARDS and the risk of aerozolisation.

Pre-oxygenation should be performed using a well fitting occlusive face-mask

A viral filter, if available (or at least a HME), must be inserted between the face-mask and manual ventilation device!

Non-rebreather masks are NOT recommended as they provide suboptimal pre-oxygenation and promote aerosolization.

Nasal oxygen should NOT be used during pre-oxygenation or for apnoeic oxygenation for the same reason.

Mechanical ICU ventilators and anaesthetic machines can be used to oxygenate and ventilate COVID-Patients. The choice will depend on their availability.

Prepare for Difficult Intubation in Advance!

Consider initial video laryngoscopy if available. Have a 'difficult airway set' ready to use if required. Keep the cardiac arrest trolley nearby.

If a supraglottic device is indicated, second-generation devices (e.g. iGel) are recommended due to their higher seal pressure.

Intubated patients should be immediately equipped with closed suction systems.

A cuff manometer should be used to measure tracheal tube cuff pressure and allow the best possible sealing.

Team Setup

Limit the number of team members in the room.

Use the most experienced clinician for airway management. Consider calling for help (e.g. senior anaesthetist).

Be sure to get 'Runners' available in the antechamber for additional help.

Personal Protective Equipment PPE

Clinician managing the airway (intubation, bronchoscopy, tube repositioning, percutaneous dilatational tracheostomy) and his direct assistants:

Impervious gown
N95/FFP2 mask
Face shield or goggle for eye protection
Surgical cap
Consider double gloves (outer gloves can be removed after airway management)

In general: all procedures that carry the risk of aerosolization should be performed wearing a N95/FFP2 face-mask. Otherwise, surgical masks are considered safe.

Follow hospital and/or WHO guidelines for both donning and doffing of PPE.

4. Extubation-Specific Recommendations

Ideally, patients should be non-infective when extubated, but this is unfeasible as resources might be drained. If there remains a risk of viral transmission, consider the following:

Patients should be ready for extubation onto face-mask
NIV and High-Flow should be avoided
Use the same level of PPE as is worn during intubation
The patient should NOT be encouraged to cough
A simple oxygen mask should be placed on the patient immediately post-extubation

Brewster DJ at al. Med J Aust; 16 March 2020

@ILCOR 2020: Let's Put the Supraglottic Airway First!

Thu, 13 Feb 2020 00:00:00 GMT

The International Liaison Committee on Resuscitation has published the last guidelines for advanced cardiac life support (ACLS) on resuscitation ILCOR in 2015. Usually, these statements are updated every five years, but 'Circulation' has now published an AHA (American Heart Association) focused update due to an increased number of studies looking at ACLS-specific interventions.

These updates are focused on three specific areas:

Advanced airway management
Vasopressors
Extracorporeal cardiopulmonary resuscitation ECPR

No News in regards to Vasopressors and ECPR

Vasopressors in Cardiac Arrest

Epinephrine (aka Adrenaline) should be administered to patients with cardiac arrest (Class I; Level of Evidence B-R)
It is reasonable to administer 1mg every 3 to 5 minutes (Class IIa; Level of Evidence C-LD)
High-dose epinephrine is not recommended for routine use in cardiac arrest

The bottom line: Great, these recommendations are no real news and do not change current guidelines at all.

Extracorporeal Cardiopulmonary Resucitation ECPR

There is insufficient evidence to recommend the routine use of ECPR for patients with cardiac arrest AND ECPR may be considered for selected patients as rescue therapy when conventional CPR efforts are failing in settings in which it can be expeditiously implemented and supported by skilled providers

The bottom line: ECPR is not for on the roads and remains an exception in general.

Advanced Airway Management

Taking recent evidence into account the updated guidelines 2019 conclude:

Either BMV or an advanced airway strategy may be considered during CPR for adult cardiac arrest in any setting (Class 2b; Level of Evidence B-R).
If an advanced airway is used, the SGA can be used for adults with OHCA in settings with low tracheal intubation success rate or minimal training opportunities for ETT placement (Class 2a; Level of Evidence B-R).
If an advanced airway is used, either the SGA or ETT can be used for adults with OHCA in settings with high tracheal intubation success rates or optimal training opportunities for ETT placement (Class 2a; Level of Evidence B-R).
If an advanced airway is used in the in-hospital setting by expert providers trained in these procedures, either the SGA or ETT can be used (Class 2a; Level of Evidence B-R).
Frequent experience or frequent retraining is recommended for providers who perform ETI (Class 1; Level of Evidence B-NR).
Emergency medical services systems that perform prehospital intubation should provide a program of ongoing quality improvement to minimize complications and to track overall SGA and ETT placement success rates (Class 1; Level of Evidence C-EO).

We Suggest: Put the Supraglottic Airway First!

In regards to these updated guidelines, the necessity of optimal cardiopulmonary resuscitation (CPR) during resuscitation and practical considerations, it seems reasonable to put the supraglottic airway (SGA) to the very top of airway management!
Here is why:

During resuscitation maintaining circulation and therefore vital coronary perfusion pressure (CPP) is the mainstay of success
BMV requires interruptions of CRP (30:2), this is deleterious!
Avoiding unnecessary interruption of compressions remains therefor a top priority. Interruptions result in the sudden collapse of CPP, which will hinder successful CPR

Avoiding interruptions is the key to successful CRP and therefore survival

Bag mask ventilation (BMV) can be quite tricky, especially when performed by untrained personnel.
BMV is NOT a secure airway; the risk of aspiration is significant!

On the other hand

While providing a 'secure' airway, successful endotracheal intubation requires skilled hands and regular training
ETI's are mostly outside the scope of practice among many doctors, nursing staff or paramedics
Intubations under CPR conditions are never easy and might be even more challenging out-of-hospital
Again, CPR is often interrupted to provide optimal conditions for endotracheal intubation

It, therefore, seems plausible to put the supraglottic airway first. Not only first as a choice of airway management, but also one of the first things to do:

Placing a supraglottic airway (SGA) is simple and straight forward. Anyone can learn this procedure in a short time. We teach ICU doctors and nurses successfully on how to use non-inflatable supraglottic airways (e.g. the i-Gel device) for CPR.
Placing an SGA is easier than simple bag-mask ventilation (BMV)!
An SGA allows continuous compressions and ventilation simultaneously - no need for deleterious interruptions
An SGA protects the airway from aspiration fairly well - some devices even allow the introduction of a small suction catheter into the stomach
Moreover, if required, endotracheal intubation can still be performed by using a bougie through the SGA. This provides another option to perform ETI without interruptions of chest compressions.
And last but not least, SGA's allow continuous measurement of end-tidal CO2

Summary of Evidence and Experience on Airway-Devices used for CRP

The International Liaison Committee on Resuscitation (ILCOR) has again carried together all evidence and recently published more than 50 new ILCOR treatment recommendations and scoping reviews. You can find these documents right here: https://costr.ilcor.org

This website provides an excellent systematic review of the Advanced Airway Management during Adult Cardiac Arrest, containing references to all relevant evidence available.

Based on this and given the experience from everyday clinical practice, it would be worth considering supplementing the recommendations as follows.

- For resuscitation performed by health care professionals (physicians, nurses, paramedics), the use of a supraglottic airway (ideally non-inflatable) as soon as possible is recommended.

2019 AHA Focused Updated on Adult Cardiovascular Life Support

Vitamin C in Sepsis - Fails!

Mon, 20 Jan 2020 10:38:31 GMT

The headlines in the news 2017 were remarkable indeed: "Doctor believes he has found the cure for sepsis..." or "Doctor says improvised 'cure' for sepsis has had remarkable results".

Dr. Paul Marik described his observation in an interview in 2017, where he mentions several cases of sepsis that have almost miraculously responded to the application of vitamin c (watch here: Interview on WAVY TV). He even continues, that since then they see "the same thing over and over again". This implicated that these results were reproducible. He finally stated that the current data at that stage were "impressive" and that there was enough basic science to show that it works.

Vitamin C has many interesting properties that theoretically could be on benefit in sepsis. (read here: Crit☁ post on Vitamin C). Its application was already proposed for the treatment of other diseases like the common cold of Influenza. Despite some moderate positive influence observed, these results could not be reproduced in trials.

While the news picked up on this story as a miracle drug, Paul Marik et al. published their results of a before-and-after single-centre, retrospective cohort study in Chest 2017. In this paper, they compared 47 patients with sepsis that received the metabolic cocktail (Vitamin C 1.5g 6-hourly, hydrocortisone 50mg 6-hourly and thiamine 200mg 12-hourly) to 47 patients which did not - notably in a non-double-blinded, non-randomized fashion. Their results showed overall hospital mortality of 8.5% with the 'cocktail' and 40.4% without its application.

This publication was reason enough to launch a small war of faith about sense and nonsense of this cocktail for sepsis.

The VITAMINS Trial - First Failure

Since 2017 a tiny bunch of studies were published, many of them with significant limitations like a small number of patients, often not randomized-controlled and with conflicting results.

Nabil Habib T, Ahmed I (2017) Early Adjuvant Intravenous Vitamin C Treatment in Septic Shock may Resolve the Vasopressor Dependence. Int J Microbiol Adv Immunol. 05(1), 77-81.

Shin et al. J Clin Med. 2019 Jan; 8(1): 102.

Fowler et al. JAMA. 2019 Oct 1;322(13):1261-1270.

Fujii et al. have just now published the first more substantial and rigorous trial taking a closer look at the influence on vitamin c in sepsis.

They performed an

international, multicenter, randomized-controlled open label trial

In which they enrolled 211 patients with septic shock admitted to an ICU.

They compared

Treatment with Vitamin C 1.5g 6-hourly IV, hydrocortisone 50mg 6-hourly IV and thiamin 200mg 12-hourly IV

to

Hydrocortisone 50mg 6-hourly IV only.

They found

No difference in time alive and time free of vasopressors (primary endpoint) and

No difference 28 days or 90 days mortality (secondary endpoint)

This first study on a larger scale, unfortunately, disappoints. More trials are on the way and might give a clearer picture of this topic to come to a final decision eventually.

For the moment it is appropriate to state:

At this stage there is NO evidence to support the routine use of Vitamin C in sepsis

Sepsis is a complex syndrome and not a disease, it is unlikely a single substance will bring simple 'cure' to all patients

Why on earth does it seem that the use of steroids are basic mainstay of sepsis treatment?

Just as a reminder: Guidelines recommend against the routine use of glucocorticoids in patients with sepsis. However, corticosteroid therapy is appropriate in patients with septic shock that is refractory to adequate fluid resuscitation and vasopressor administration.

Fujii et al. JAMA. Published online January 17, 2020. doi:10.1001/jama.2019.22176

7 Reasons for the Use Vasopressors through Peripheral Catheters

Mon, 16 Dec 2019 03:19:38 GMT

Teaching in medical school and opinions in literature are in agreement: The application of vasopressors requires central venous access. The reason for this are concerns that vasopressors given over a peripheral venous catheter (PCV) may cause phlebitis or even worse necrosis or ischemia through extravasation.

While irritation of a peripheral vein is often observed with the administration of drugs like potassium or amiodarone, this usually is not the case with the application of, e.g. norepinephrine. Besides, it is essential to keep in mind that the insertion of a central venous catheter (CVC) is technically demanding and takes a certain amount of time when performed correctly. The procedure is also associated with potentially dangerous complications that might be hazardous to the patient.

Therefore a fundamental question arises:

Do all patients that require vasopressors need a central venous catheter?

What about the peripheral access (PVC) - Any dangers there?

Study #1

In 2015 Cardenas-Garcia et al. have published a

open-label, single-centre trial

in which they treated

a total of 734 patients with the vasopressors noradrenaline (506), dobutamine (101 and phenylephrine 176 via peripheral access only.

The average duration of infusion was 49 hours.

They found

extravasation in only 2% of all patients without any further tissue injury following treatment with local phentolamine injection and nitroglycerin paste.

These findings indicate that:

Correctly applied vasopressors via a peripheral line are safe, even if given over several hours
Complications like extravasation are generally rare and are unlikely to cause any further harm

J Hosp Med. 2015 Sep;10(9):581-5. doi: 10.1002/jhm.2394. Epub 2015 May 26.

Study #2

In 2015 Loubani et al. performed a systematic review of extravasation and local tissue injury from the administration of vasopressors through peripheral intravenous catheters and central venous catheters. They looked at

Local tissue injury close to the infusion site
Extravasation of a vasopressor into surrounding tissue or a body cavity
Major disability of the patient

An excellent summary of this study can be found on REBELEM, who correctly states that this review was only for complications from administration of vasopressor, and not a review of the frequency of complications (i.e. instances where no complications occurred).

This review shows nicely though that

Most complications concerned peripheral IV-lines distal to the antecubital or popliteal fossae, and
Almost all occurred in infusions running for more than 4 hours

J Crit Care. 2015 Jun;30(3):653.e9-17. doi: 10.1016/j.jcrc.2015.01.014. Epub 2015 Jan 22

Study #3

In 2017 Lewis at al. performed a retrospective chart review of 202 patients who received vasopressors through a PVL. The primary vasopressors used were norepinephrine and phenylephrine. The most common PVL sites used were the forearm and antecubital fossa. The incidence of extravasation was 4%. All of the events were managed conservatively; none required an antidote or surgical management. Although with many limitations to this review, there is further evidence indicating:

Extravasation seems to be a rather rare complication and again did not result in any further harm for the patient

J Intensive Care Med. 2017 Jan 1:885066616686035.

Study #4

In 2018 Medlej et al. tried to determine the incidence of complications of running vasopressors through PIVs in patients with circulatory shock in a prospective, observational trial. Again, REBELEM has nicely summarized this rather small trial. It is another small indicator that:

In patients with shock, the use of peripheral vasopressors (noradrenaline and dopamine) in a large bore PVC at a proximal site for less than 4 hours is safe!

J Emerg Med. 2018 Jan;54(1):47-53.

Well, how do PVC's compare to CVC's then?

Study #5

In 2018 Ricard JD et al. performed a

Multicenter, controlled, parallel-group, open-label randomized trial

in which

Patients were randomized to receive central venous catheters (135 patients) or peripheral venous catheters (128 patients) as initial venous access.

The primary endpoint was the rate of major catheter-related complications within 28 days.

They found significantly more PVC-related complications per patient when only treated with peripheral lines compared to patients that received at least one CVC.

And they concluded: "central venous catheters should preferably be inserted: a strategy associated with less major complications"

REALLY? Hold on! - let's have a close look at those 'major complications, the PRIMARY endpoint of this study!

Although going through this article several times, it remains difficult to understand how PVC insertion difficulties are comparable major complications.
First of all, difficult venous access is one of the indications for the insertion of a CVC, not its complication. Patients were randomly allocated in a one-to-one ratio to receive a CVC or a PVC. So how can difficult peripheral access be a complication when going for central access directly?

Also, there is considerable doubt whether the occurrence of a pneumothorax can be used to compare complications of these two procedures!

However, when eliminating difficult peripheral access as an indication, there is not much left to say PVCs are associated with more complications than CVCs. Moreover, most clinicians will agree that catheter infections in PVCs are less problematic than when occurring in CVCs.

Given these considerations, it seems safe to say:

In critically ill patients peripheral access can be tricky indeed
PVCs might be associated with more frequent local erythema and extravasation of fluids
Good to know: peripheral access is not associated with more pneumothoraces ; )

Crit Care Med. 2013 Sep;41(9):2108-15

2019 - More Evidence Keeps Rolling In!

Study #6

Tian et al. have performed a

Systematic review

in order to assess

the frequency of complications associated with the delivery of vasopressors via PVCs.

They included

Studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. This resulted in seven observational studies (only) with a total of 1384 patients.

They found that

Extravasation occurred in 3.4% (95% CI 2.5-4.7%) of patients. There were no reported episodes of tissue necrosis or limb ischaemia. All extravasation events were successfully managed conservatively or with vasodilatory medications.

Extravasation seems to be an issue with PVCs, but there is no further information on the size or location of the peripheral line.
Again, no serious side effects were reported, indicating that peripherally administered vasopressors are safe over all when given for a limited duration.

Emerg Med Australas. 2019 Nov 7.

Study #7

Pancaro et al. published

a retrospective cohort study

in which identified

14'385 surgical patients who received peripheral norepinephrine infusions perioperatively with a concentration of 20 µg/mL (a rather low concentration)

They found

Extravasation of norepinephrine in only 5 patients and there where zero related complications requiring surgical or medical intervention. The median time of norepinephrine infusion among these patients was 20 minutes.

This is a fairly good indicator that:

Giving vasopressors through PVC for a limited duration is safe

Extravasation might actually be harmless when applied in rather lower contentrations

Anesthesia & Analgesia. SEPTEMBER 27, 2019

Giving the current evidence available, it seems appropriate to conclude:

The need for vasopressors itself is not a mandatory indication for central venous access

Vasopressors can be safely given through a peripheral venous catheter
- This is especially true when used for a limited time (e.g. less than 4 hours) and when applied in rather lower concentrations.

In the critically ill central venous access will inevitably still be required (advantage of multiple lumens, difficult peripheral access, other drugs that do entitle the use of a CVC etc.)

Novel Approach to SVT's: Single Syringe Adenosine!

Wed, 04 Dec 2019 09:29:06 GMT

Supraventricular tachycardias (SVT) typically refer to tachydysrhythmia arising from above the level of the bundle of His and usually present as a small complex tachycardia. A classification based upon a narrow QRS-complex is useless though as this is also dependent on any pre-existing bundle branch block.

SVT's can be classified a follows

Regular Atrial
Sinus tachycardia
Atrial tachycardia
Atrial flutter
Inappropriate sinus tachycardia
SNRT

Irregular Atrial
Atrial fibrillation
Atrial flutter with variable block
Multifocal atrial tachycardia (MAT)

Regular Atrioventricular
AVRT
AVNRT
Automatic junctional tachycardia

AV nodal re-entry tachycardia (AVNRT) is the most common cause of palpitations in patients with structurally normal hearts and mostly occurs spontaneously or triggered (e.g. exercise, caffeine etc.)

Although usually well tolerated, SVT's can become a potentially life-threatening condition.

Treatment with Adenosine

The American Heart Association 2015 guidelines for Adult Advanced Cardiac Life Support recommends adenosine in non-hypotensive patients with regular narrow complex SVT. Adenosine is an endogenous purine nucleoside that blocks atrioventricular nodal conduction via the A1 receptors in the cardiac tissue. That is why the use of adenosine causes transient asystole, which in turn very often produces a sense of 'impending doom' or a feel that one is about to die.

With a half-life less than 10 seconds, cardioversion can be performed quickly, and side effects usually are limited and short-lasting.

Due to these kinetics, 6 mg of adenosine are classically administered as a rapid intravenous bolus followed by a 20ml saline flush. If the first dose fails to restore normal sinus rhythm, another 12 mg of adenosine are recommended. This can be repeated one more time if necessary. As adenosine and normal saline are mostly applied over a 2-way stop-cock, this procedure might result in a suboptimal application for technical reasons.

Did you know: If adenosine is given over a central line, its dose should be halved!

The Single Syringe Adenosine-Trial

Wouldn't it be great, to simply mix your adenosine into the syringe with the saline flush and administer the 'cocktail' as one? Well, this is exactly what Marc McDowell at al. did.

They performed

a small prospective study

of

53 hemodynamically stable adults who presented to a single emergency department with SVT

patients were given

6 mg of adenosine one of two ways: in a single syringe combined with 18 mL of saline (26 patients) or in two separate syringes, one containing adenosine and the other 20 mL of saline (27 patients)

They found:

More patients in the single-syringe group than the two-syringe group converted to sinus rhythm after the first dose (73.1% vs. 40.7%)

By the way: This is not the first study looking into mixinf adenosine with normal saline. Choi et al. have already mixed 6mg of adenosine with 15ml of normal saline and found a comparable conversion rate compared to the 'conventional' method.

Although both studies show several limitations, there are some important information we can get:

- Concern that diluting adenosine into normal saline maight impair the drug's efficacy is not justified

- Administering adenosine and normal saline in one syringe is safe and at least equaly effective

- This 'Single Syringe'-technique ist technically safer and should be considered in this setting

I personally will will be going down this path from now on.

McDowell M, Mokszycki R, Greenberg A, et al. Single Syringe Administration of Diluted Adenosine. Acad Emerg Med. 2019 Oct 30.

Choi SC, Yoon SK, Kim GW, et al. A convenient method of adenosine administration for paroxysmal supraventricular tachycardia. J Korean Soc Emerg Med 2003;14(3):224-7.

Antidote Pocket Cards - In Deutsch!

Sat, 09 Nov 2019 16:00:08 GMT

Die Pocket-Cards 'Toxine und Antidots' stehen nun frei zum Download zur Verfügung. Sie wurden als praktische Hilfe für den klinischen Alltag in Deutsch zusammengestellt und können auch als pdf weiter unten bezogen werden.

Feedback und Anregungen jederzeit gerne in den 'comments'!

Download die Pocket Cards hier:

Pocket Cards Toxine und Antidots
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