Recently, there has been a significant increase in influenza cases, vulnerable groups such as the elderly, patients with chronic obstructive pulmonary disease, diabetes and cancer patients are prone to severe disease after infection, anti-influenza measures have always been in a race against the evolution of influenza and genetic mutations, and it is difficult for us to outperform its genetic mutations, so there have been four major influenza outbreaks, H1N1 in 1918, H2N2 in 1957, H3N2 in 1968, and H1N1 outbreak in 2009, which is relatively close to us.
The outbreak of influenza is closely related to everyone, for severe influenza, it is difficult to generalize influenza as a severe type, many influenza patients in the severe stage are not simply influenza infection, but influenza itself can also cause severe disease.
流感“重”症能否等同于流感“终”症？
We have just admitted a 95-year-old woman who was still able to walk instead of stay in bed one week after a femoral neck fracture, and did not have a significant cough or sputum production, only a symptom of "loss of appetite". CT showed widespread effusion in both lungs (below) and decreased oxygenation, so we were faced with a dilemma, at such an advanced age of 95, intubation or not? As society ages, it is inevitable that we will have to treat such patients.
It should be noted that severe influenza is not a "terminal illness" of influenza in the terminal stage, and under the leadership of many critically ill respiratory teachers, our treatment level is constantly rising.
The following is a case of "severe influenza" in 2014, a 73-year-old male with a fever and cough for 7 days and hypertension for 20 years. Diagnosis: severe pneumonia, ARDS, admission: FiO2 100% PO2 52mmHg.
After more than 20 days, the patient developed barotrauma and was diagnosed with H7N9. CT is the image of day 1 (left) and day 25 (right).
We left some pathologies and found that after more than 20 days of changes, the pathological changes in the patient's lungs far exceeded our expectations, the formation of transparent membrane, thrombosis and a large number of inflammatory cell infiltration, such lungs have been unable to ventilate normally, and more terrible is found through Actin staining, the patient not only has a severe inflammatory infiltration, but also fibrosis (blue part), which suggests that it is "flu terminal", the end of the terminal stage.
After 4 years, this is a case in 2018, a female 9 years and 11 months old with a fever of six days and a cough of five days. On day 10 of admission, PCR showed H5N6 (+). On the first day, I was found to have lobar pneumonia on one side, but after continuous treatment, and even went to ECMO, the child's pulmonary fibrosis was still out of control, and we did not want to see such an outcome.
Figure: Lung images on day 1 (left) and day 25 (middle and right).
Regarding the treatment of severe influenza, I think firstly, we need early diagnosis and lock the etiology to a certain species, secondly, use some necessary antiviral drugs early, and finally, in the process of severe treatment, we should not take detours to avoid irreversible changes and pathophysiological interstitial fibrosis changes, we believe that a small amount of fibrosis is not visible on imaging, but it does not mean that it does not exist in pathology. From three days onwards, the patient's fibrosis begins to change after oozing.
2023-2024 Severe Influenza Case Update, How to "Stop the Car" and Prevent Severe Illness from Happening?
Today, I will mainly share with you what are the new characteristics of severe influenza cases in 2023-2024. After preliminary and incomplete research, I found some differences between post-COVID and pre-COVID severe influenza cases, and we had to discuss the interrelationship between influenza and COVID-19, co-infections such as influenza and mycoplasma, and the key steps in the development of severe illness caused by influenza...... This is so that we can "stop the car" and prevent serious illness from happening.
Because there really isn't much we can do after a severe illness. In terms of prevention, we are calling for a move away from full testing, no more reliance on drug prophylaxis, and some new measures, such as lowering the price of testing, making testing more accessible, and even making health insurance accessible to more people, and I think that's something we can work on right now.
This is the case we saw in the outpatient clinic, a 31-year-old female patient, due to "Sjögren's syndrome" oral hormones in July and August 2023, had fever in September, Tmax 39°C, negative respiratory pathogenology, CT showed pneumonia (left in the figure below), and was treated with cephalosporin infusion for 1 week, intermittent cough after infusion in October, no fever, and re-examination CT (right in the figure below), recurrence of illness in December, low-grade fever for 1 week, oral azithromycin was ineffective, and external hospital tests showed positive influenza A antigen and Mycoplasma pneumoniae IgM+.
The picture below shows the patient's family, the purple part is the Sjögren's syndrome patient, who is also the mother of the child, who was negative for pneumonia and respiratory etiology on September 17, and the influenza A virus antigen + and Mycoplasma pneumoniae IgM+ on December 25, the pink part is the child, and the influenza B virus antigen + and mycoplasma IgM+ on December 20, and the child's father was also positive for influenza A virus antigen on September 25, which shows that co-infection and familial cluster infection are inevitable.
Against this backdrop, the severe cases we see must be difficult cases. Next, I would like to report on a few representative cases of this year.
Case 1: Diabetic patients with influenza A + lung gram mixed infection
This patient had a lung g-g infection that we least wanted to see in the ICU, an elderly man, 69 years of age, with acute onset. He was admitted to the hospital with "cough and sputum for 2 days and dyspnea for 1 day". Previous diabetes mellitus, history of atrial fibrillation for more than 1 year, no oral medication. Predominantly respiratory symptoms, acute pulse oxygen drops, combined with severe atrial fibrillation and rapid ventricular rate, make oxygenation more difficult to correct.
In the process of disease evolution, on November 29, he developed cough, sputum, white sticky sputum, and did not go to the hospital for treatment, and on December 1, he had a fever of 38.4°C, accompanied by a little hemoptysis, accompanied by shortness of breath, and chest tightness, and the chest CT scan of the local hospital showed that the right lung was infected, and then the patient was short of breath, and was intubated and connected to a ventilator to assist breathing, and the pulse oxygen continued to be maintained at about 82%. On the same day, he was sent to the emergency department of our hospital, and the tracheal intubation was mechanically ventilated, and the examination was complete: chest CT + pulmonary artery CTA, cardiac color ultrasound, blood routine + CRP, BNP, cardiac enzymes, and coagulation arterial blood gas analysis.
Physical examination: temperature: 36.9°C, pulse: 111 breaths/min, blood pressure: 112/73 mmHg (norenal) 23 breaths/min, SPO2 90% (endotracheal intubation connected to ventilator, FiO2 100%).
Ancillary tests: chest CT + pulmonary artery CTA: no obvious abnormalities in the CTA of the main pulmonary artery and its main branches, poor visualization of the distal branches, double pneumonia (the right lung is the disease), re-examination after treatment is recommended, slight local distension of the aortic arch, coronary artery and aortic sclerosis. Cardiac enzymes: serum troponin T: 0.033ng/nL↑, serum myoglobin: 160ng/mL ↑, N-terminal forebrain natriuretic peptide: 2170ng/L↑, blood count: white blood cell count: 1.38×109/L↓, neutrophil count: 0.86×109/L↓, lymphocyte count: 0.47×109/L↓, CRP: 35.30mg/L↑; bedside ultrasound: left atrial slightly enlarged, ventricular septum slightly thickened, left ventricular systolic function normal low value, EF Blood gas analysis: PaO2 88.7, PaCO2 42, Lac 4.7, K+ 3.1.
It can be seen that the imaging evaluation showed that there was indeed a double pneumonia mainly on the right side, and the lymphocytes were 0.47×10^9/L in the routine blood examination, which was consistent with the manifestations of viral infection, and his heart and kidney reserve function were also poor.
Photos: Chest CT, cardiac ultrasound (2023/12/1)
In this case, a diagnosis of severe influenza pneumonia appears appropriate, but it is uncertain whether this is the only problem.
Admission diagnosis
1. Severe influenza pneumonia, 2. Respiratory failure, 3. Sepsis, 4. Diabetes mellitus, 5. Atrial fibrillation, 6. Coagulation dysfunction, 7. Acute renal insufficiency.
Recognized organ support techniques such as non-invasive, invasive, and ECMO have been developed in the ICU, and the purpose of using them is to stabilize oxygenation and allow further etiological clarification. After admission, the patient was treated: 1. endotracheal intubation, ventilator-assisted ventilation, 2. norenal-to-renal maintenance of blood pressure, 3. sedation and analgesia, and 4. meropenem anti-infection.
At 16:46 on December 1, V-V ECMO was put on the machine, and the right femoral vein and right internal jugular vein were placed with ECMO catheters. ECMO parameters: blood flow rate 4.11 L/min, gas FiO2 100%, gas flow 4 L/min. Ventilator parameters: oxygen concentration 40%, PEEP: 8cmH2O, tidal volume 410ml.
On the 4th day of admission, tracheoscopy and flexible bronchoscopy were performed on December 4, and a few bleeding points were found on the mucosal surface at the carina, more jelly-like secretions were found in the left and right lumens to block the lumen, and more bloody secretions were found on the right side, which were fully suction and lavage, and the examination was routine, culture, etc. were sent for further screening of the etiology, and the lumen was significantly smoother than before after treatment, but there were still a large number of sputum plugs in the right small bronchi.
After a short period of antiviral treatment with neuraminidase inhibitors, influenza A quickly turned negative, but soon Klebsiella pneumoniae appeared, fortunately, it was sensitive lung gram, this process caught us off guard, and we were routinely given sensitive carbapenems, and at the same time continued to give oseltamivir treatment, and stopped after the nucleic acid of influenza A turned negative.
Figure: X-ray changes in the lungs during ECMO, from left to right: 12.1 chest x-ray: right pneumonia, 12.3 chest x-ray: right pneumonia, roughly similar to 12.1, small effusion in the right pleural cavity, 12.5 chest x-ray: right pneumonia, slightly absorbed from 12.3.
Figure: Trends of WBC, BNP, PCT, CRP, arterial blood lactate, and EF at cardiac ultrasound during ECMO
Prone ventilation, protective ventilation, appropriate cardiac protection were performed, and we remained concerned about septic cardiomyopathy or even fulminant myocarditis during this period. We noticed a sharp increase in BNP on the third day, so when managing multi-organ failure secondary to viral pneumonia, it is necessary to consider that the heart is likely to develop rapid manifestations of heart failure, and if myocardial infarction is ruled out, it must be that the myocardial cells are severely damaged, and the inflammatory factors are also gradually and rapidly improved based on the improvement of oxygenation and lung protection. EF was transiently reduced to 30% on cardiac ultrasound, and even some AKI manifestations were comorred, and prone positioning and protective ventilation avoided the further occurrence of spontaneous breathing-related lung injury and mechanical ventilation-related lung injury.
Figure: Follow-up lung X-ray after ECMO weaning, (left) 12.7 Chest x-ray: right pneumonia, similar to 12-5, right pleural effusion, (right) 12.14 Chest x-ray: right pneumonia, progressed from 12.7
Figure: 12.28 Chest CT was re-examined, and the range of double pneumonia was reduced and the density was increased compared with the previous (2023-12-1), and the re-examination was carried out after treatment. The aortic arch is slightly distended, the mediastinal is more often and the lymph nodes are slightly larger, and the coronary arteries and aorta are sclerosis.
The patient also underwent bedside rehabilitation exercises and his condition has been completely stabilized.
In this case, the patient may seem to have the flu, but in fact the flu may be just a trigger, but it is actually mixed with many other conditions, such as diabetes, pulmonary infection, etc. Studies have found that 30% of influenza hospitalized patients have "diabetes", which may manifest as pneumonia, tracheitis, sinus infection, ear infection, the acute process of influenza may exacerbate the rise in blood sugar, and the continuous decline in appetite of the disease may lead to a sharp drop in blood sugar, so blood sugar management challenges, foreign CDC has a guideline, if diabetic patients are expected to have influenza, what items do they need to prepare? including sports drinks, juices and snacks to regulate blood sugar.
Influenza and diabetes can create a "vicious circle of each other", which we do not want to see, and influenza vaccination is still the most reliable means of prevention and control. Antiviral drugs given within 48 hours of symptom onset are beneficial for diabetic patients (high-risk), and drugs such as oseltamivir and baloxavir should become routine drugs for diabetic patients. A study evaluating the cost and cost of health resources for the benefit of using antiviral drugs in diabetic patients found that once these antiviral drugs were given, the annual cost/emergency department admission/hospitalization/hospital stay decreased significantly (left in the figure below), especially in the first and fourth quarters (right in the figure below), the cost of patients and the proportion of emergency department admissions decreased sharply, so the importance of early use of antiviral drugs was re-emphasized.
A basic study suggests that Klebsiella pneumoniae infection activates an immune response that reduces influenza-induced lung damage.
The following figure shows the comparison of the distribution and composition of bacteria in the lower respiratory tract of severe pneumonia (influenza + VS influenza-), the most common infection is Acinetobacter baumannii, and the proportion of Klebsiella pneumoniae in influenza-negative people is higher than that in influenza-positive people, which is the data of Beijing, and other regions should also combine local epidemiological data.
Case2：慢阻肺RSV+甲流混合感染
This is an elderly man, 74 years old, admitted to the hospital for "coughing and wheezing for more than 50 years, exacerbation with confusion for 1.5 hours", previous history of "hypertension", long-term oral amlodipine besylate + losartan potassium hydrochlorothiazide, and previous pulmonary function tests confirmed COPD. In the past week, there were frequent ventricular premature contractions, betalux sustained-release tablets 47.5mg/day, and "atorvastatin" 20mg/night treatment.
Evolution of the disease: cough, sputum, wheezing for more than 50 years, often in autumn and winter and after cold, yellow purulent sputum, asthma aggravation, can be improved after anti-infection treatment, previous pulmonary function tests confirmed COPD. He is usually treated with long-term home oxygen therapy (LTOT). On November 27, 2023, the symptoms of cough, sputum production, and asthma worsened, accompanied by fatigue, and he was admitted to the hospital without special treatment. After returning home, self-measured SpO2 70-80%, self-oxygen inhalation symptoms could not be improved, gradually appeared breathless, 1.5 hours later sent to the emergency room of our hospital, coma, SPO2 66%, dyspnea, cyanosis of the skin and mucous membranes, and immediate invasive mechanical ventilation. Urgent blood gas analysis, CT of the head and chest.
Emergency examination in our hospital: blood gas analysis (FiO2 61%): PH 7.062 PaO2 57.4mmHg, PaCO2 undetectable, Lac 3.8mmol/L, K+ 4.0mmol/L, blood routine: white blood cell count: 17.73×10^9/L↑, neutrophil count: 11.18×10^9/L↑ Hypersensitive C-reactive protein: 33.13mg/L↑, RSV: positive for IgM antibody, chest CT ( 2023/11/27): Chronic inflammation of both lungs, emphysema, bullae, multiple bronchiectasis in both lungs.
Admission diagnosis
1. Chronic obstructive pulmonary disease with acute exacerbation (AECOPD), 2. Type II respiratory failure, 3. Pulmonary encephalopathy, 4. Cardiac arrhythmia, 5. Frequent premature ventricular contractions, 6. Frequent premature atrial contractions, 7. Hypertension grade 3 (very high risk), 8. Severe influenza.
We tested positive for RSV during treatment, followed by influenza A, and 4 or 5 days after treatment, even with neuraminidase preparations, influenza A virus remained positive. In the treatment plan, invasive mechanical ventilation with endotracheal intubation, volume-controlled mode, PEEP 5cmH2O, FiO2 60%, VTE 563ml, piperacillin sodium tazobactam sodium + peramivir anti-infection, methylprednisolone sodium succinate 40mg qd, reduced to 20mg qd on December 5 (discontinued on 12-7 days), fiberoptic bronchoscopic sputum aspiration and alveolar lavage on December 1. For the patient's proponation, 1. ipratropium bromide + bubudine sonic nebulized inhalation; 2. doxofylline.
Even though the patient's carbon dioxide level did not reach the normal level, considering the patient's poor lung function and high probability of co-infection, the endotracheal intubation was removed on December 5, and the non-invasive mask-assisted ventilation (P-SIMV mode, FiO2 40%, PEEP 5cm H2O) was rechecked, and the blood gas was rechecked at night, with a pH of 7.367, PaO2 168mmHg, PaCO2 61.6mmHg, and Lac 1.6mmom/L. From December 6th to 7th, the non-invasive mask and nasal high-flow humidified oxygen therapy (FiO2 40%, flow rate 60L/min) were applied sequentially. On December 8, it was completely changed to nasal high-flow humidified oxygen therapy.
On December 8, he re-examined chest CT and found emphysema and bullae in both lungs. Chronic inflammation of both lungs increased slightly from November 27. Multiple bronchiectasis in both lungs, infection in the right lower lung, progression earlier, bilateral pleural effusion. Calcification of the aortic arch and some coronary artery walls.
After about 10 days of antiviral treatment, on December 12, the virus finally turned negative, and it seems that the virus has been negative for a longer time in such patients. Therefore, if there is a monoclonal antibody option for RSV treatment, we may have more to look forward to.
During the hospitalization, the patient's symptoms gradually improved and his consciousness became clearer. On December 20, high-flow oxygen therapy was changed to nasal cannula oxygen (3L/min), and the SpO2 was maintained at 95-96%; on December 21, there was no obvious shortness of breath and no fever in the resting state, and the respiratory symptoms improved significantly, and the blood routine white blood cell count was rechecked within the normal range, and the hospital was discharged. After discharge, long-term home oxygen therapy.
Figure: The trend of total white blood cell count and neutrophil percentage, the trend of PaO2 (left) and PaCO2 (right) in arterial blood gases, the trend of PH and Lac in arterial blood gases, and the trend of inflammatory markers during hospitalization
Summary of this patient:
In terms of drug treatment, it is mainly to improve airway resistance, expectorant, anti-infection, antiviral, and anti-asthma.
It is necessary to pay attention to the choice of extubation timing: patient 11.27 tracheal intubation was connected to ventilator ventilation for a total of 8 days, accurately grasped the timing of extubation, removed the tracheal intubation in time, and then changed to non-invasive ventilation and sequential application of high-flow oxygen therapy, gradually transitioned to high-flow oxygen therapy (12.8), and finally changed to nasal cannula oxygen (12.20), and the patient's respiratory function gradually recovered, improved and discharged.
In addition, although the patient's symptoms have improved significantly, he has been suffering from carbon dioxide retention, and combined with the patient's 50-year history of COPD, he still needs to rely on long-term home oxygen therapy to improve the prognosis after discharge.
Influenza is a common cause of acute exacerbations of COPD, and seasonal influenza vaccines (annual) are internationally recognized to prevent COPD exacerbations, however, studies on the mortality rate and comorbidities of influenza vaccination in patients with COPD exacerbations are not yet available in large-scale studies.
The clinical classification of influenza virus infection COPD includes: 1. asymptomatic infection, 2. fulminant primary viral pneumonia, 3. secondary bacterial pneumonia, and the severity of influenza virus infection depends on the type of virus, many host factors, age, comorbidities such as cardiopulmonary disease, etc., which determine whether patients with COPD are likely to worsen to severe disease or require mechanical ventilation in the ICU. Vaccines and new antiviral drugs have brought us opportunities to reduce the burden of COPD and influenza. However, once seasonal influenza mutates, it is easier to spread between people and people, especially avian influenza, once the transmission from animals to humans begins to intensify, it can become a catastrophic event.
The previous belief that the primary cause is bacteria has changed, but the literature now believes that respiratory viral infections are associated with 40-60% exacerbations of COPD, and the pathogenesis and impact of influenza virus infections in COPD still need to be further studied.
Studies have shown that 23.8% of chronic lung diseases over the age of 65 will die from influenza, 9% of patients with chronic lung diseases ≧ 65 years old will die from influenza virus and RSV infection, and the hospitalization rate of patients with chronic lung diseases who have not received influenza vaccine is twice that of vaccinated patients.
To be continued, in the next issue, Professor Guo Qiang will continue to share 3 cases of "influenza" - refractory hypoxemia in cancer patients, myocarditis cardiac arrest in young patients, which diagnosis and treatment experience and clinical research suggest? In the face of foggy and multi-system respiratory tract infection, if it is not "influenza", what kind of diagnosis should be considered?
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Expert presentation
Guo Qiang
Doctor of Medicine, Chief Physician, Professor, Academic Doctoral Supervisor, Director of Institute of Critical Care Medicine, Soochow University, Vice President of the Fourth Affiliated Hospital of Soochow University, Chairman of Bacterial Infection and Drug Resistance Prevention Branch of Suzhou Medical Association, National Talent Program, "Changjiang Scholar" of the Ministry of Education Professor Tegang, Key Medical Talent of Jiangsu Province, Advanced Individual in the Prevention and Control of the New Coronary Pneumonia Epidemic in the National Health System, Captain of the Second Team of National Support for Wuhan and Suzhou, Key Health Talent of Gusu, Vice Chairman of the Youth Committee of the Respiratory Branch of the Chinese Medical Doctor Association, Deputy Head of the Respiratory Rehabilitation Group of the Chinese Medical Association, Member of the Respiratory Disease Branch of the Chinese Preventive Medicine Association, Member of the Influenza Prevention and Control Branch of the Chinese Preventive Medicine Association.
* This series of live broadcasts was hosted by Dr. Wang Yimin, Assistant Director of the Department of Respiratory and Critical Care Medicine at China-Japan Hospital.
This article was edited and typeset by Jerry, editor of Breathe
Thank you Roche for your strong support for this season's live broadcast
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Editor-in-charge: Jerry