HFMD is an acute infectious disease caused by enteroviruses (CoxA16 and EV71), mostly occurring in preschool children, with the highest incidence in the under-3 age group. It is transmitted mainly through the gastrointestinal tract, respiratory tract and close contact. The main symptoms are papular rash and herpes on the hands, feet and mouth. In a few cases, meningitis, encephalitis, encephalomyelitis, pulmonary edema and circulatory disorders may occur, mostly caused by EV71 infection, and the main cause of death is cardiopulmonary failure due to brainstem encephalitis.
I. Diagnostic criteria
(A) Clinical diagnosis and staging
Stage 1 (Hand, foot and mouth rash stage)
Fever, rash (maculopapular rash, papular small herpes) on hands, feet, mouth and buttocks, which may be accompanied by cough, runny nose, loss of appetite and other symptoms.
Some cases present only with a rash or herpetic pharyngitis, and individual cases may have no rash.
The majority of cases in this stage are common cases of HFMD, and most of them are cured within one week, with a good prognosis.
Phase 2 (neurological involvement phase)
In a few cases, central nervous system manifestations appear within 1-5 days of the disease course, such as poor mental performance, drowsiness, easy startle, headache, vomiting, irritability, limb tremors, acute limb weakness, cervical ankylosis and other signs and symptoms of meningitis, encephalitis, poliomyelitis-like syndrome, encephalomyelitis, signs: meningeal irritation sign (+), diminished or absent tendon reflexes or hyperactive tendon reflexes, positive pathological signs.
Special examinations
Increased cerebrospinal fluid pressure, leukocytosis, normal or mildly increased protein. CT scan of the cerebrospinal cord may have no positive findings, and MRI may show abnormalities (damage to the brainstem or gray matter of the spinal cord).
Stage 3 (pre-cardiopulmonary failure)
It occurs mostly within 5 days of the disease, and is characterized by increased heart rate and respiration, cold sweats, skin pattern, cold extremities, elevated blood pressure, elevated blood glucose, elevated peripheral blood white blood cells (WBC), and abnormal heart ejection fraction.
Stage 4 (cardiopulmonary failure stage)
Neurogenic pulmonary edema and circulatory failure. It occurs mostly within 5 days of the disease, and the age is predominantly 0-3 years. Tachycardia (bradycardia in some children), shortness of breath, cyanosis of lips and mouth, coughing of pink foamy sputum or bloody fluid, persistent blood pressure decrease or shock. In some cases, severe cerebral failure is the main manifestation, and pulmonary edema is not obvious, with frequent convulsions, severe consciousness impairment and central respiratory and circulatory failure.
Phase 5 (recovery period)
Body temperature gradually returns to normal, dependence on vasoactive drugs gradually decreases, symptoms of neurological involvement and cardiopulmonary function gradually recover, and a few may remain with neurological sequelae symptoms.
(II) Critically ill cases
One of the following conditions occurs.
1. frequent convulsions, coma, brain herniation. Brain
2. dyspnea, cyanosis, bloody foamy sputum, pulmonary rales, etc. lung
3, Shock and other signs of circulatory insufficiency. Heart
(iii) Confirmed cases
Clinical diagnosis cases with positive nucleic acid test specific for enterovirus (CoxA16, EV71, etc.).
II. Principles of treatment in each phase
Phase 1
No need for hospitalization, mainly symptomatic treatment, attention to isolation, avoid cross-infection, proper rest, light diet, good oral and skin care. Outpatient physicians should inform parents of children to observe carefully and to seek immediate medical attention in case of early manifestations of severe EV71 infection.
Phase 2
Admit to general ward, treatment must be timely, once diagnosed, immediately administer medication, use dehydrating diuretics such as mannitol to reduce intracranial hypertension; control fluid intake appropriately; apply gammaglobulin as appropriate for cases with persistent high fever, manifestations of spinal cord involvement or rapid disease progression. Closely observe the temperature, respiration, heart rate, blood pressure and changes in skin temperature of the extremities and other high-risk factors that may develop into critical type, especially for cases within 3 years of age and within 5 days of the disease.
(1) Control intracranial hypertension.
(1) Limit fluid intake (60-80 ml/kg, d) (including the amount of food or nasal feeding).
(2) Mannitol 0,5-1,0g/kg?times, every 2-8 hours, 20-30 minutes intravenously, adjust the interval of drug administration and dose according to the condition.
(2) Apply intravenous immunoglobulin as appropriate: total 2g/kg, divided into 2-5 days.
(3) Apply glucocorticoids as appropriate:
Reference dose: methylprednisolone 1~2mg/(kg?d), dexamethasone 0,2~0,5mg/(kg?d). A few people with severe disease and rapid progress can be treated with glucocorticoid shock therapy: methylprednisolone 15-30mg/kg,d (the maximum single dose does not exceed 1g), there is still some controversy about the application of high-dose glucocorticoid shock therapy.
Stage 3
Admission to ICU, based on phase 2 treatment, blocking sympathetic excitability, timely application of vasoactive drugs, such as milrinone and phentolamine, along with oxygen therapy and respiratory support. Apply gammaglobulin and glucocorticoids as appropriate. Prophylactic application of antibacterial drugs is not recommended. Milrinone: loading dose of 50ug/kg, 10 minutes slow static push; maintenance dose of 0,25-0,75ug/kg, min (Milrinone is preferred when the heart rate is fast and blood pressure is high, but it is prohibited when the blood pressure is low), depending on the condition, it can also be started directly from the maintenance dose.
Phase 4
Early application of ventilator with positive pressure ventilation or high frequency ventilation on the basis of phase 3 treatment. In cases of pulmonary edema and pulmonary hemorrhage, positive end-expiratory pressure (PEEP) should be increased appropriately; frequent aspiration is not advisable. Dopamine, dobutamine, epinephrine, and norepinephrine may be used in patients with hypotensive shock. In cases of severe cardiopulmonary failure, extracorporeal membrane oxygenation may be considered.
(1) Vasoactive drugs
①Dopamine: 5-20ug/kg, min.
②Dobutamine: 2-20ug/kg, min.
③Norepinephrine: 0.02-1ug/kg, min.
④Adrenaline: 0.05-2ug/kg, min.
(2) Suggested ventilator initial adjustment parameters (selected according to pulmonary edema and pulmonary hemorrhage)
①Oxygen concentration: 80% to 100%.
②PIP: 20～30cmH2O.
③PEEP: 4～8cmH2O.
④Respiratory rate: 20～40 times/min.
⑤Tidal volume: 6～10ml/kg.
Adjust ventilator parameters at any time according to blood gas and X-ray chest film results.
(3) Appropriate application of sedative drugs.
①Phenobarbital: loading dose 10-15mg/kg?d, intravenous or intramuscular injection.
②10% chloral hydrate: 0,5ml/kg?d, enema.
③ Valium: 0, 3 to 0, 5mg/kg?d; maximum dose: 30 days-5 years, 5mg/d; over 5 years 10 mg/d (slow static push, note respiratory depression). About 1 mg for 1 year
④Imidazolam: 0,1mg/kg?times intravenous push once, 0,3~0,5mg/kg?h maintenance.
III. Other symptomatic treatment
(1) Cooling: ibuprofen, physical cooling, subcooling (especially head cooling protection), etc.
(2) Monitor blood glucose, if blood glucose >13,0mmol/L in q2h, use insulin 0,03-0,05U/kg,h continuous pumping to maintain blood glucose in normal range, pay attention to blood glucose should not fall too fast; if blood glucose <2,80mmol/L, use 10%-25% glucose 0,5-1g/kg,times.
(3) Myocardial protection: Fructose diphosphate sodium (FDP) 100-250 mg/kg, d IV.
(4) Inhibition of gastric acid: cimetidine, omeprazole.
(5) Supraventricular/ventricular tachycardia: Amiodarone (5-10 mg/kg, injected within 30 min, followed by 5-10 mg/kg, d maintenance intravenous drip.
(6) Stabilize the internal environment and correct acid-base imbalance and electrolyte disturbance.
IV. Case observation and management
1.Early identification points of severe cases
(1) Persistent high fever does not subside.
(2) Poor mental health, vomiting, easily startled, shaking limbs, weakness.
(3) Increased respiration and heart rate.
(4) Cold sweating, poor peripheral circulation.
(5) Hypertension.
(6) Significant increase in peripheral blood leukocyte count.
(7) Hyperglycemia.
2.Referral of serious cases Serious cases should be referred to higher level designated hospitals while establishing intravenous access to local hospitals with dehydrating agents and hormones.
3.Categorize and manage patients
Classify patients according to their conditions (ordinary, serious and critical cases) and centralize them in designated wards, which is more conducive to the observation of their conditions.
4.Strengthen ward inspection
The main items of inspection include: body temperature, consciousness, respiration, heart rate, blood pressure, terminal circulation of the extremities, etc., and make records. The ward inspection of general cases should be conducted every 4-6 hours, and if early manifestations of severe cases are found, they should be transferred to the intensive care ward for treatment and observation in time. If critical cases are found, they should be transferred to ICU ward for resuscitation and ventilator in time. A tabular format can be used to fill in the main observation items.