Hypoxia;

How should I generally go about treating my non-ICU hospitalized patient with newly diagnosed Covid-19 and who doesn’t require more than conventional O2?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Much of the management of Covid-19 hospitalized patients who don’t require ICU care and need no more than conventional 02 (ie, high-flow or mechanical/non-mechanical ventilatory support) depends on the severity of their disease: “mild/moderate” (eg, SpO2≥94% on room air) vs “severe” (eg, Sp02<94% on room air) disease; respiration rate ≥30/min and lung infiltrates on chest radiograph>50% may also be considered, but I personally find these parameters less reliable.  Generally, patients hospitalized with Covid-19-related symptoms (respiratory or otherwise) require specific treatment to keep them from progressing or succumbing to their disease (see Figure below). 1-5

In patients with mild/moderate Covid-19, the first step is to determine whether they are at low risk (ie, NO risk factors) or high risk (ie, ≥1 risk factors) of progression to severe disease.  Recall that there are numerous risk factors for progression, including age (eg, ≥50 y) and many comorbidities, such as diabetes, chronic kidney disease, obesity, smoking (current or former), disability (eg, wheelchair dependence), and mental health disorders (eg, depression), just to name a few.1 If your patient with mild/moderate Covid-19 has ANY Covid-related symptoms and ANY risk factors for progression, you should strongly consider IV remdesivir. If your patient’s admission has nothing to do with Covid-19 but qualify for anti-Covid treatment, an oral anti-viral regimen (eg, nirmatrelvir-ritonavir [Paxlovid]) used for ambulatory patients may also be considered (see related pearl on P4P). If your patient has NO risk factors for progression to severe disease, symptomatic treatment is all that’s needed.

If your patient has severe disease but no need for 02 supplementation, IV remdesivir and prophylactic heparin (either fractionated [eg, enoxaparin] or unfractionated) should be considered; no need for dexamethasone or systemic steroids in this situation.

If your patient has severe Covid-19 and needs supplemental 02, you should consider initiation of remdesivir, dexamethasone and, at the minimum, prophylactic anticoagulation with either a fractionated or unfractionated heparin product as soon as possible.  Use of therapeutic anticoagulation in this setting (ie, outside of ICU) is controversial with NIH guidelines recommending therapeutic heparin for those with elevated D-dimer without increased bleeding risk (CIIa, “weak” with moderate supportive evidence).2,6,7  You may also be able to forgo systemic steroids in your patient with minimal 02 requirement (ie, 1-2 L) per NIH, particularly if immunocompromised, as hypoxia in such patients may be more related to viral infection itself and not significant inflammatory reaction.

If your patient with severe Covid-19 gets progressively worse requiring high-flow oxygen or non-invasive ventilation outside of ICU, you should consider adding baricitinib as a first line immunomodulator (tocilizumab or others in NIH guidelines as an alternative)2 in patients who are not already immunocompromised or do not already have and are not at high risk of secondary infections.

The duration of remdesivir treatment in hospitalized patients is usually 5 days (or until discharge) for severe Covid-19, and 3 days for those with mild/moderate disease. The ultimate duration should be individualized in patients at risk of ongoing viral replication.  One retrospective study in immunocompromised patients hospitalized for Covid-19 found remdesivir to be effective in reducing hospitalization and mortality when initiated within 2 days of hospitalization and given for a median of 5 days, even among those not requiring 02 supplementation or requiring only low flow 02.

Couple more things to keep in mind when managing severe Covid-19. When indicated, remdesivir should be given ideally as early as possible and no later than 10 days after onset of symptoms and dexamethasone should be given for up to 10 days or until discharge.  Anticoagulation, prophylactic or therapeutic, should only be prescribed in the absence of any contraindications for bleeding (see Figure footnote) and continued until discharge for no more than 14 days total.

As with all drugs, please make sure you are thoroughly familiar with the dosing, adverse effects and contraindications to above-referenced medications before prescribing them.

Figure. Management of SARS-CoV-2 positive hospitalized patients requiring no or only conventional 02 due to Covid-19

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References

  1. CDC. Interim Clinical Considerations for COVID-19 Treatment in Outpatients | CDC. Accessed Feb 1, 2024
  2. NIH. Clinical Spectrum | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024
  3. Uptodate. Coived-19 management in hospitalized patients. https://www.uptodate.com/contents/covid-19-management-in-hospitalized-adults. Accessed Feb 5, 2024.
  4. Bash K, Sacha G, Latifi M. Covid-19: A management update. Clev Clin J Med 2023;90:677-683. https://www.ccjm.org/content/90/11/677
  5. Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir reduced mortality in immunocompromised patients hospitalized for Covid-19 across variant waves: Findings from routine clinical practice. Clin Infect Dis 2023; 77;1626-34. https://pubmed.ncbi.nlm.nih.gov/37556727/
  6. Merz LE, Fogerty AE. The conundrum of anticoagulation for hospitalized patient with Covid-19. NEJM Evidence 2023;2 (2).  https://evidence.nejm.org/doi/full/10.1056/EVIDe2200329
  7. ATTACC, CTIV-4a, REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in noncritically patients with Covid-19. N Engl J Med 2021; 385:790-802. https://pubmed.ncbi.nlm.nih.gov/34351721/

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How should I generally go about treating my non-ICU hospitalized patient with newly diagnosed Covid-19 and who doesn’t require more than conventional O2?

How often is the liver affected by Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Abnormal liver enzymes in patients with Covid-19 are common, particularly in those with severe disease.

 
Elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported in 14-53% of patients in several case series. More severe cases appear to have a higher prevalence of AST elevation (1). As some cases also have elevated creatine kinase (CK), the relative contribution of muscles to these enzyme abnormalities is unclear (2).

 
A small study involving ICU patients with Covid-19 reported a prevalence of elevated AST of 62% compared to 25% in non-ICU patients (3). Other studies have confirmed lower incidence of AST abnormality among patients with mild or subclinical disease (4,5).

 
Although much of the published reports of liver injury in Covid-19 have revolved around AST and ALT abnormalities, gamma-glutamyl transferase (GGT) may also be elevated. GGT was abnormal in 54% of patients with Covid-19 during their hospitalization with alkaline phosphatase elevation reported in ~2.0% (1, unpublished reports). Elevation of total bilirubin has also been reported occasionally (1).

 
Although the exact mechanism(s) of Covid-19-related is unclear, direct viral infection of liver cells is one possibility as viremia has been documented in some cases (1). Of interest, a related coronavirus, SARS-CoV-1 has been shown to infect liver tissue and cholangiocytes may express ACE2 receptors, a prime target for Covid-19 virus (1,6,7, unpublished reports).

 

Despite these observations, to date, viral inclusions have not been demonstrated in the liver. Other possible causes of liver injury in Covid-19 include innate immune dysregulation, cytokine storm, hypoxia and drugs (1,2).

 

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References
1. Zhang C, Shi L, Wang FS. Liver injury in COVID-19:management and challenges. Lancet Gastroenterol Hepatol 2020; March 4. https://doi.org/10.1016/S2468-1253(20)30057-1
2. Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern. Lancet Gastroenterol Hepatol 2020;March 20. https://doi.org/10.1016/52468-1253(20)30084-4
3. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. https://pubmed.ncbi.nlm.nih.gov/31986264/
4. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. N Engl J Med 2020;published online Feb 28. DOI:10.1056/NEJMoa2003032
5. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020; published onlineFeb 24. DOI:10.1016/S1473-3099(20)30086-4 (lancet 8)
6. Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 209-nCoV infection. bioRxiv 2020;published online Feb 4. https://doi.org/10.1101/2020.02.03.931766.
7. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; published online Feb 18. DOI:10.1016/S2213-2600(20)30076-X

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

How often is the liver affected by Covid-19?

My patient with diverticular bleed has now developed signs of bowel ischemia with abdominal pain and sepsis after transcatheter colic artery embolization. Is bowel ischemia common after embolization of lower gastrointestinal (GI) arteries?

FA Manian MD, MPH, , , , , , , , Leave a comment

It may be more common than we think! Reported rates of bowel ischemia following lower GI artery embolization have been as high as 22% (1,2). For this reason, it is prudent to closely monitor for signs of bowel ischemia and infection in patients who undergo embolization to control lower GI bleeding.

In some cases, ischemia of the bowel appears to be mild enough to be treated conservatively, while in other cases bowel infarction with surgical intervention has been necessary (1).  One case report described signs of infection (including fever, abdominal tenderness and leukocytosis) 2 days after arterial embolization in a patient who was treated conservatively (3), while another described “sepsis” 6 days post procedure with bowel wall ischemia requiring surgical resection (1). 

Bowel injury leading to a septic picture following embolization of lower GI arteries should not be surprising given the expected capillary hypoperfusion and risk of tissue hypoxia.  Compared to embolization for upper GI bleed, lower GI embolization may place the patient at higher risk of bowel ischemia bowel ischemia due to lack of a rich collateral blood supply (1).  Older patients may also have mesenteric artery atherosclerotic disease or low cardiac output,  further compromising the collateral blood flow (3).  

At a more molecular level, hypoxia leads to the activation of hypoxia-inducible factor (HIF-1), which plays an important role in inducing gut injury. In fact, deletion of HIF-1a in mice prevented shock-induced intestinal permeability and bacterial translocation that ultimately led to bacteremia (4). 

As for preventing embolization-induced bacteremia, although antibiotics are used for liver and spleen embolization prophylaxis, their role in colic angioembolization is unclear (5).  

Bonus Pearl: Did you know that some of the earliest angioembolizations were performed during the Vietnam War to stop bleeding from bullet injuries? (6)

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References:

  1. Gady, J, Reynolds, H., & Blum, A. Selective arterial embolization for control of lower gastrointestinal bleeding: Recommendations for a clinical management pathway. Current Surg 2003; 60: 344-347. https://www.sciencedirect.com/science/article/abs/pii/S0149794402007493
  2. Rossetti A, Buchs NC, Breguet R, et al. Transarterial embolization in acute colonic bleeding: review of 11 years of experience and long-term results. Int J Colo Dis 2013;28:777-782. https://link.springer.com/article/10.1007/s00384-012-1621-5
  3. Shenoy, S, Satchidanand, S, & Wesp S. Colonic ischemic necrosis following therapeutic embolization. Gastrointest Radiol 1981, 6: 235-237. https://link.springer.com/article/10.1007/BF01890256
  4. Vollmar, B., & Menger, M. Intestinal ischemia/reperfusion: Microcirculatory pathology and functional consequences. Langenbeck Arch Surg 2011; 396: 13-29 https://link.springer.com/article/10.1007%2Fs00423-010-0727-x 
  5. Ryan, J. Mark, Ryan, Barbara M, & Smith, Tony P. Antibiotic prophylaxis in interventional radiology. JVIR 2004; 15: 547-556. https://www.sciencedirect.com/science/article/pii/S1051044307603248
  6. Nolan, T, Phan H, Hardy A, et al. Bullet embolization: Multidisciplinary approach by interventional radiology and surgery. Semin Interven Radiol 2012, 29: 192-6. https://www.ncbi.nlm.nih.gov/pubmed/23997411 

Contributed by Hannah Ananda Bougleux Gomes, Medical Student, Harvard Medical School, Boston, MA.

My patient with diverticular bleed has now developed signs of bowel ischemia with abdominal pain and sepsis after transcatheter colic artery embolization. Is bowel ischemia common after embolization of lower gastrointestinal (GI) arteries?

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?

FA Manian MD, MPH, , , , , , Leave a comment

Any respiratory rate (RR) greater than 20/min in an adult patient may be cause for concern, particularly in the setting of potentially serious disease and absence of an obvious cause such as pain or fever.

Our patient’s RR is outside the commonly cited normal range of 12-20/min. It indicates increased alveolar ventilation which may in turn be caused by hypoxia, hypercapnea, or metabolic acidosis, all portending possibly poor outcome, if left untreated.1  It’s no surprise that an abnormal RR is often the first sign of clinical deterioration.2 RR is also the least likely of the vital signs to be affected by polypharmacy (eg, NSAIDs affecting temperature, beta-blockers affecting heart rate and blood pressure). 

Another reason for not dismissing an RR of 22 in our patient is the common practice of guessing rather than measuring the RR by healthcare providers in part likely due to the  more “labor-intensive” nature of measuring RRs compared to other vital signs and lack of appreciation for its importance in assessing severity of disease. 1 Of note, in an experimental study of doctors viewing videos of mock patients, over 50% failed to detect abnormal RR when using the “spot” technique of estimating without a timer.3 Even when presented with a RR of 30/min, over 20% of doctors reported it as normal (12-20/min)!

Final tidbit: Do you want to know what a RR of 20/min really feels like? Take a breath every 3 seconds.  If you are like most, it doesn’t feel “normal”!

References
1. Cretikos MA, Bellomo R, Hillman K. Respiratory rate: the neglected vital sign. MJA 2008;188:657-59. https://www.ncbi.nlm.nih.gov/pubmed/18513176
2. Flenady T, Dwer T, Applegarth J. Accurate respiratory rates count: So should you! Australas Emerg Nurs J 2017; 20:45-47. https://www.ncbi.nlm.nih.gov/pubmed/28073649
3. Philip KEJ, Pack E, Cambiano V et al. The accuracy of respiratory rate assessment by doctors in a London teaching hospital: a cross-sectional study. J Clin Monit Comput2015;29:455-60. https://www.ncbi.nlm.nih.gov/pubmed/25273624

My previously healthy 55 year old patient is admitted with a respiratory tract infection and a respiratory rate of 22 breaths/min. Should I be concerned?