Interview with Professor Ren Qian: Diabetes combined with "new crown critical illness", seizing the "golden window" of antiviral drugs

Introduction: At present, the situation of the new crown epidemic is still grim, and many endocrinologists have gone to the front line
of the fight against the new crown.
Diabetes is the number one disease in endocrinology, and there are many elderly patients, and patients are more likely to progress to critical illness
after being infected with the new coronavirus.
At the same time, the high incidence of acute complications of diabetes adds difficulties
to disease management.

The Department of Endocrinology of Peking University People's Hospital is in a leading position
in the clinical diagnosis and treatment of endocrine and metabolic diseases and research.
Since December 2022, the Department of Endocrinology of Peking University People's Hospital has begun to actively admit patients with endocrine diseases and severe new crown diseases, Professor Ren Qian has rich clinical management experience in critical endocrine diseases, and Yimaitong is honored to invite Professor Ren Qian to participate in an exclusive interview to share valuable diagnosis and treatment experience on the management of diabetes combined with new crown critical diseases.

Biography

Ren Qian

• He is currently the deputy chief physician, associate professor, doctor of clinical medicine, and master supervisor of the Department of Endocrinology, Peking University People's Hospital

• Vice Chairman of the Youth Committee of the 5th Committee of the Endocrinologist and Metabolism Physician Branch of the Chinese Medical Doctor Association

• Youth Committee Member of Endocrinology Branch of Beijing Medical Association

• Member of the Islet β Cytology Group of the 9th Committee of the Diabetes Branch of the Chinese Medical Association

• Member of the editorial board of the Chinese edition of the British Medical Journal (BMJ) and the young editorial board member of the Chinese Journal of Diabetes

• His research interests include diabetes genetics and pharmacogenetics
  .
  He has presided over or participated in a number of national research projects, and published more than 10 SCI articles in journals such as Diabetologia, JCEM, and Thyroid as the first author

Yimaitong: Hello Professor Ren, what is the reception of critically ill patients in the endocrinology ward?

Professor Ren Qian: Hello everyone, I am Dr
.
Ren Qian from the Department of Endocrinology, Peking University People's Hospital.
The Department of Endocrinology of Peking University People's Hospital admitted the first patient
with severe new coronary pneumonia and diabetes around mid-December.
Since then, the number of severe cases admitted has increased rapidly, and about 60%-70% of the wards are now critically ill
.
The situation in the wards is still at its peak, but the number of critically ill cases admitted to the emergency department is declining
.

In general, the proportion of patients with severe disease who have diabetes is large
.
On the one hand, it may be related to the high prevalence of diabetes in China (the prevalence of diabetes in Chinese adults is 12.
8%); On the other hand, after diabetic patients combined with the new crown, under the influence of multiple factors, they are prone to acute complications, such as diabetic ketoacidosis or hyperosmolar hyperglycemia
.

Medical Pulse: What are the key points to pay attention to in the management of diabetes combined with new crown critical illness?

Professor Ren Qian: Diabetes combined with new crown critical illness is divided into two situations: one is that there are no acute complications of diabetes; The other is the emergence of acute complications of diabetes, which brings more challenges
to clinical treatment.

In general, we need to manage
the disease in terms of antiviral therapy, anti-inflammatory therapy, glycemic management, nutritional support, monitoring of inflammatory indicators, monitoring of vital signs, respiratory support, etc.

1.
Seize the "golden window" of antiviral treatment

If the patient's onset is less than 5 days, we will give Paxlovid (nimatevir/ritonavir) antiviral therapy to seize the "golden window"
of antiviral therapy.

Note the combination of Paxlovid with other drugs: since both nirmatevir and ritonavir are substrates of CYP3A, any drug that affects the activity of CYP3A metabolizing enzymes will alter the metabolism of nirmatevir and ritonavir, thereby affecting their efficacy and safety
.
In addition, ritonavir itself is a potent inhibitor of irreversible CYP3A, which can increase the plasma concentration of other CYP3A substrates, thereby enhancing the efficacy of the combination drug or increasing the risk
of adverse reactions.
Therefore, these drugs should not be used
in combination with drugs that are highly dependent on CYP3A clearance and whose elevated plasma concentrations cause serious and/or life-threatening adverse effects.
Do not combine with potent CYP3A inducers, as this can result in a significant decrease in plasma concentrations, possibly resulting in loss of virologic response and potential resistance
.

About the combined use of Paxlovid with hypoglycemic drugs:

➤Can be combined with acarbose, metformin, gliclazide, glimepiride, glipizide, insulin, canagliflozin, dapagliflozin, empagliflozin, sitagliptin, linagliptin, vildagliptin, liraglutide, dulaglutide, exenatide, semeglutide;

➤ When combined with saxagliptin, it is recommended that saxagliptin 2.
5mg/d;

➤When combined with glibenclamide, nateglinide, and repaglinide, it is recommended to monitor blood glucose and adjust the dose
if necessary.

For the combined use of Paxlovid with other drugs: see the attached table
at the end of the text.

2.
Anti-inflammatory therapy

Due to the sufficient evidence in foreign studies, for severe or critically ill patients, our department chooses dexamethasone
for anti-inflammatory treatment.
Considering its obvious glycemic effect, we usually choose 5mg/d for drug dosage, intravenous administration, generally continuous medication for 5~10 days
.
During this period, we monitor changes in inflammatory markers, and in most patients we discontinue oral hypoglycemic agents and switch to insulin to control blood glucose
.

➤If the absolute value of lymphocytes rises and inflammatory factors (such as C-reactive protein, interleukin 6, ferritin) decrease, it proves that the treatment effect is better, and the dose can be considered to be reduced to 2.
5mg/d, and the drug can be stopped after a few days of continued medication;

➤ If symptoms worsen despite hormone therapy in critically ill patients, we may consider tocilizumab or baricitinib
.
Usually in patients with high levels of interleukin 6, tocilizumab will have a better
therapeutic effect.

3.
Anticoagulant therapy

In patients with severe disease, we consider giving therapeutic doses of low molecular weight heparin
in the absence of contraindications.
Anticoagulation therapy
is also considered if the patient has a high risk factor for severe disease (diabetes itself is a high risk factor for severe disease, in addition, including age > 65 years old, not fully vaccinated against the new crown, accompanied by cardiovascular and cerebrovascular underlying diseases, obesity, heavy smoking, etc.
) or medium-sized cases with rapid progression.

4.
Blood sugar management

As mentioned earlier, the use of dexamethasone can lead to a significant increase in blood sugar, so it is necessary to strengthen blood glucose monitoring and management
during this period.
Practical experience:

➤ If the patient has received insulin therapy before, and the new coronavirus infection type is severe and requires dexamethasone treatment, we will adjust the insulin treatment regimen to the basic combined mealtime mode, and for patients who eat normally, we will appropriately increase the insulin dose, especially the dose of insulin during meals;

➤ If the patient has previously received oral hypoglycemic drugs and the new coronavirus infection type is severe and requires dexamethasone treatment, we recommend discontinuing oral drugs and using insulin to control blood glucose
instead.
Because severe patients often have hypoxaemia or respiratory failure, metformin
is discontinued to avoid the risk of lactic acidosis.
For patients with a medium-sized new coronavirus type, oral drugs including metformin can be continued to be used
.

5.
Management of acute complications of diabetes

For patients with concomitant diabetic ketoacidosis (DKA) or diabetic hyperosmolar hyperglycaemic state (HHS), the principles of treatment include aggressive fluid replacement, correction of dehydration, intravenous insulin infusion to control blood glucose, correction of water, electrolyte, and acid-base imbalances, and removal of precipitating and therapeutic complications, of which fluid replacement is the first measure
.


Regarding the rehydration speed, type of rehydration and rehydration amount, if the patient has no cardiorenal insufficiency, the rehydration speed will be appropriately accelerated at the beginning, and then the rehydration speed will be adjusted
according to the patient's blood sodium, urine output, blood pressure, etc.
For rehydration types, we would prefer 0.
9% normal saline
.
Taking HHS as an example, we will estimate the amount of fluid replacement in 24 hours, about 6-10 liters, and if the patient is older and has cardiorenal insufficiency, we will adjust the rehydration volume
accordingly.


In practice, we consider giving fluids to patients through both intravenous and digestive tract access
, taking into account the patient's actual situation.
If the patient is in a coma (more common in critically ill patients), nasogastric feeding by tube is considered
.

6.
Nutritional therapy

Since patients tend to have poor appetite or are in a coma, nutritional support is very important
for critically ill patients.
Especially in patients with diabetic ketoacidosis, ketosis due to insufficient caloric intake is difficult to correct.

In patients who are completely unable to eat, enteral nutrition
via gastric tube is considered.
The specific plan is to divide the total daily calorie into four or five meals of nasogastric tube nasal feeding
.

For glycaemic management, subcutaneous basal insulin combined with insulin during meals prior to nasogastric feeding may be considered; For patients with concurrent DKA or HHS, intravenous insulin pumps are recommended for glycaemic
control.

7.
Respiratory support

Respiratory support is very important in the management of severe virus infection, and can be judged whether respiratory support is in place
by monitoring the patient's respiratory rate, oxygen saturation, oxygenation index, etc.
If nasal cannula oxygen is given and oxygen saturation remains below 93% or oxygenation index ≤ 300 mmHg, consider upgrading to a mask, and upgrade to a noninvasive ventilator for patients with an oxygenation index below 200 mmHg, with ongoing monitoring
.

8.
Indicator monitoring

In addition to infection-related indicators, clinical monitoring of comorbidities-related indicators, such as blood pressure, intake, DDimmer, changes in renal function (eGFR), changes in heart-related indicators (BNP, TnI, electrocardiogram, echocardiography, etc.
), ketone body level, electrolyte balance (blood sodium, blood potassium), blood albumin level, hemoglobin, etc
.

Schedule: Paxlovid Drug Interactions

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