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Clinical Practice Guideline - Management of COVID-19 in Adults

2020


AbbreviationsABGACE

ACLFAKI

ARBARDS

BiPAP

BNPCAPD

CBCCHF CKDCK-MB

CLDCOVID-19COPD

CRPCTECGeGFR

HBVHCV

HCQIATA

ICAO

LDHLFTLPM

MAPMDI

MDRMRSA

NMBANIPPV

OHS

OSAPEEP

PPPPEPplatPTT/INR

PTSDPOCUSqSOFA

QTcRFTROSCRT-PCR

SARISARS CoV-2

SOFA

sPO2

TNFUFHWHOVTM

Arterial blood gasAngiotensin converting enzymeAcute-on-chronic liver failureAcute kidney injury

Angiotensin receptor blockerAcute respiratory distress syndromeBi-level positive airway pressureBrain natriuretic peptideContinuous ambulatory peritoneal dialysis

Complete blood countCongestive heart failureChronic kidney diseaseCreatinine kinase - MB

Chronic liver diseaseCorona virus disease 2019Chronic obstructive pulmonary diseaseC-reactive proteinComputed tomographyElectrocardiographyEstimated glomerular filtration rateHepatitis B virusHepatitis C virus

HydroxychloroquineInternational air transport associationInternational civil aviation organizationLactate dehydrogenaseLiver function testLiters per minute

Mean arterial pressureMetered-dose inhaler

Multidrug-resistantMethicillin-resistant staphylococcus aureusNeuromuscular blocking agentNon-invasive positive pressure ventilationObesity hypoventilation syndromeObstructive sleep apnea Positive end-expiratory pressureProne positionPersonal protective equipmentP-plateau pressureProthrombin time/ International normalized ratioPost-traumatic stress disorderPoint of care ultrasonographyQuick sequential Organ Failure AssessmentCorrected QT intervalRenal function testReturn of systemic circulationReverse transcription polymerase chain reactionSevere acute respiratory illnessSevere acute respiratory syndrome corona virus-2Sequential Organ Failure AssessmentPeripheral capillary oxygen saturationTumor necrosis factorUnfractionated heparinWorld health organizationViral transportation medium


Guideline Authors

Guideline Reviewers

Dr. Fathimath Nadiya, MD, Senior Consultant in Internal MedicineDr. Abdullah Isneen Hilmy, MD, Consultant in Internal Medicine, IGMHDr. Mohamed Faisham, MD, Consultant in Internal Medicine, IGMHDr. Zeena Mohamed Fuad, DrIntMed, Consultant in Internal Medicine, IGMHDr. Mohamed Sunil MIntMed, Consultant in Internal Medicine, National Cardiac Center, IGMHDr. Sariu Ali Didi, FCP(SA), Consultant in Internal Medicine, IGMHDr. Ismail Latheef MD, Consultant in Anesthesiology, IGMHDr. Zulaikha Maee MD, Consultant in Anesthesiology, IGMHDr. Dusooma Abdul Razzag MD, Consultant in Anesthesiology, ADK HospitalDr. Asadh Mohamed Shaheed MBBS, Medical officer, IGMH

Dr. Abdul Azeez Yoosuf FRCP, Senior consultant in Internal MedicineDr. Ali Latheef MD, Senior Consultant in Internal Medicine and Head of Department of Internal Medicine, IGMH Dr. Ali Nazeem MD, Senior Consultant in Internal Medicine and Director of medical services, IGMH

Dr. Mohamed Aseel Jaleel MD, Senior Consultant in Obstetrics & Gynecology and Head of Department of Obstetrics & Gynecology, IGMH

Dr. Moosa Hussain MD, Consultant in Pulmonology, National Centre for Respiratory Medicine Dr. Ahmed Shaheed, MIntMed, Consultant in Internal Medicine, IGMH

Dr. Muaz Moosa, DrIntMed, Consultant in Internal Medicine, IGMH Dr. Nasheeda Saeed, DrIntMed, Consultant in Internal Medicine, ADK Hospital

National Cardiac Centre, IGMH

Guideline Layout & Cover Design: Hussain Shazif Adam, Creative Director, Encreare


Contents247888899999991010111112131414151515151616171717181919222222242525 26

AbbreviationsContents1 Introduction2 Case Definition 2.1 Suspected case: 2.2 Probable case: 2.3Confirmedcase:3 Diagnosis 3.1 RT-PCR 3.2 Serology 3.3Samplecollection 3.3.1 Type of Specimen: 3.3.2 PPE and ICP Measures: 3.3.3 Sample technique (Oropharyngeal) 3.3.4 Sample technique (Nasopharyngeal) 3.3.5 Collection Medium 3.3.6 Sample Transportation 3.4 Chest Radiography 3.5ComputedTomography 3.6 Lung ultrasonography4 Clinical Classification 4.1Asymptomatic 4.2Milduncomplicatedillness 4.2 Mild Uncomplicated illness 4.2.1 Management of mild uncomplicated illness 4.2.2 Discharge Criteria 4.3MildComplicatedillness 4.3.1 Management of mild complicated illness 4.3.2 Discharge criteria 4.4MildPneumonia 4.4.1 Management of Mild Pneumonia 4.4.2 Discharge criteria 4.5SeverePneumonia 4.5.1 Management of severe pneumonia 4.5.2 Discharge criteria 4.6AcuteRespiratoryDistressSyndrome 4.6.1 Management of ARDS 4.6.2 Discharge criteria 4.7 Sepsis and Septic Shock 4.7.1 Diagnosis of Sepsis and Septic Shock 4.7.2 Management of patients with sepsis and septic shock


3030303131323335373639414141414242434343

4444

45

4660

5 Complications of COVID-19 5.1 Acute kidney injury 5.2LiverDerangementsinCovid-19 5.3Neurologicalcomplications 5.4Hematologicalcomplication 5.5CardiacComplications 5.6 Cardiac Arrest 6 Intubation 6.1 Sedation 6.2Weaningoffventilator 6.2.1 Protocol for Extubation in ICU 7 Special considerations in management of COVID-19 7.1 Geriatric Age Group 7.2PatientswithMultipleComorbidities 7.2.1 Patients with Cardiovascular Diseases. 7.2.2 COPD and Chronic lung disease 7.2.3 Obesity and OHS 7.2.4 Patients with cancer and immunosuppressive state 7.2.5 Chronic kidney disease in COVID -19 7.2.6 Consideration for Liver Disease patients in the

management of COVID-19. 7.3CaringforpregnantwomenwithCOVID-19 7.4CaringforinfantsandmotherswithCOVID-19:IPCand

breastfeeding8 Mental health aspects of COVID-19 and care of patients with

psychiatric conditions.9 Palliative Care and Symptoms control in terminally ill COVID-19 patientsReference


IntroductionCorona Virus Disease 2019 (COVID-19) is an infectious disease caused by a novel corona virus – Severe Acute Respiratory Syndrome Corona Virus-2(SARS COV-2). The first case of the disease was reported in Wuhan City, the capital of Hubei Province of China, in December 2019, where a cluster of pneumonia cases of unknown aetiology had alerted WHO. A week later, the cause for these pneumonia cases was identified as SARS COV-2 infection. The resulting illness from SARS COV-2 infection was officially named COVID-19 on February 11, 2020.

Since its initial outbreak in Wuhan, COVID-19 has spread exponentially around the globe. On January 30, 2020, the disease was declared a public health emergency of international concern. Later, it was declared as a pandemic by the World Health Organization on March 11, 2020.

Prior to COVID-19 reaching pandemic level, the Maldives began preparing for a possible COVID-19 outbreak in January 2020, by conducting a risk assessment and forming a national response guideline and a health emergency coordination committee.

The Maldives confirmed its first imported case of COVID-19 on March 7, 2020, as an employee of a resort tested positive for the virus, who was a foreign national. Following this, the government further strengthened precautionary measures including stringent temporary restrictions on the tourism industry, as a preventive measure against the spread of COVID-19. On March 12, 2020, for the very first time in the Maldivian history, a 30-day state of public health emergency was declared by the Minister of Health, Mr Abdulla Ameen.

The first confirmed COVID-19 case of local transmission was reported on April 15, 2020. Since then, the total number of confirmed cases had increased drastically to 475 by May 1st, 2020. Of these cases, 18 were imported and the rest were local transmissions. These COVID-19 positive cases comprise of 150 Maldivians and 325 foreign nationals. Out of the foreigners, initial cases 13 were tourists and the remaining 312 were migrant workers. Noteworthy to mention that a large number of mingrant labourours are becoming infected due to overcroweded migrant worker dormitories. The confirmed cases include 4 pregnant women, 12 pediatric patients. Eldest patient was aged 80, while youngest was 2yrs of age. As of May 1st, 2020, most patients have presented with mild to moderate disease symptoms. However, first COVID-19 death was reported on April 29th, 2020, involved a 82yrs old female with unlderying multiple combobidities. Till date, a total of 17 cases have recovered from the illness.

With evidence of community transmission and the increasing trend of cases in the Maldives, the need for guidance for the health care providers in the clinical management of COVID 19 is of utmost importance. Healthcare workers must be protected from acquiring SARS COV-2 when they are providing clinical care. Strict use of Personal Protective Equipment (PPE) and employing concepts of telehealth has proven to be beneficial in this aspect. Similarly, emphasis on the mental health and wellbeing of the healthcare personals working on the frontline of a pandemic situation, possibly for the first time in their life, is crucial and must be considered by the higher management authorities.

As the COVID-19 is a new disease with rapidly evolving knowledge of the clinical presentation and management, there are no proven definitive treatment as of yet. However, there are multiple agents under investigation, of which Remdesivir has recently shown promising results.

This guideline is intended for health care providers, and it is based on what is currently known about COVID-19. It is composed using the most updated evidence and adapted for the optimal management of COVID-19 patients in the Maldives with the resources available in the country. Therefore, we intend to periodically review and update this guideline as more evidence becomes available. This guideline is not, however, intended to replace clinical judgement, but rather to complement it.

1


Case Definition (1)

2.1 SUSPECTED CASE

2.2 PROBABLE CASE

2.3 CONFIRMED CASE

a. A patient with acute respiratory illness (fever* and at least one sign/symptom of respiratory disease

(e. g. cough, shortness of breath),

AND

a history of travel to or residence in a location reporting local transmission of COVID-19 case within 14 days before symptom onset.

OR

b. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case in the 14 days prior before the onset of symptoms

OR

c. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e. g. cough, shortness of breath AND requiring hospitalization) AND

An absence of an alternative diagnosis that fully explains the clinical presentation.

*Absence of fever does NOT exclude viral infection

a. A suspected case for whom the report from laboratory testing for the COVID-19 virus is inconclusive

OR

b. A suspect case for whom testing could not be performed for any reason

A person with laboratory confirmation of infection with the COVID-19 virus, irrespective of clinical signs and symptoms

2


DiagnosisThe diagnosis of Covid-19 is usually based on the detection of SARS-CoV-2 by means of polymerase-chain-reaction (PCR) assay. However, new rapid antigen/antibody- based ELISA tests are currently in the pipeline which may be used in the future.

3

3.1 RT-PCR

3.2 SEROLOGY(2)

RT-PCR test should be done for all suspected cases.

If the initial testing is negative, but the suspicion for COIVD-19 remains, it is recommended for re-sampling and testing from multiple respiratory tract sites.

COVID-19 Rapid Test qualitatively detects IgG and IgM antibodies to SARS-CoV-2 in human whole blood, serum and plasma samples. This test applies lateral flow immuno-chromatography and is a tool to assist in the diagnosis of SARS-CoV-2 infections.

The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.

Specific IgM antibodies to SARS-CoV-2 can become detectable 3-5 days after onset of illness, but the intensity of this response varies between patients.

3.3 SAMPLE COLLECTION(1)

3.3 .1 TYPE OF SPECIMEN

3.3.2 PPE AND ICP MEASURES

3.3.3 SAMPLE TECHNIQUE (OROPHARYNGEAL)

• Lower respiratory specimens are preferred as it has a higher diagnostic value.• Lower respiratory specimens: sputum, endotracheal aspirate, or bronchoalveolar lavage

fluid.• Upper respiratory tract samples: nasopharyngeal aspirate or combined oropharyngeal

and nasopharyngeal swabs if not possible for a lower respiratory tract sample.

• Use Gloves, Surgical Mask, Goggles / Eyeshield and long-sleeved Gowns.• Use N95 mask with goggles, gloves and gowns if collected under aerosol-generating

generating procedures (tracheal aspiration, bronchoalveolar lavage or by sputum induction).

• Fluid resistant gown: if anticipating increased fluid exposure.

• Hold the tongue out of the way with a tongue depressor• Insert the oropharyngeal swab into the posterior pharynx and tonsillar areas rub swabs

over both tonsillar pillars and posterior oropharynx• Avoid swabbing the soft palate and do not touch the tongue with the swab tip• Place the swab immediately into a VTM (Viral Transportation Medium).


Figure 2 Nasopharyngeal Swab

3.3.5 COLLECTION MEDIUM• Nasopharyngeal/Oropharyngeal swab: Swabs used for influenza sampling• Lower respiratory samples: sterile container• Use VTM for transportation and the oropharyngeal and nasopharyngeal swab may be kept

in the same VTM.• If there is a delay in transportation, samples can be kept in a fridge at 2-8 ̊C upto ≤5 days.(2)

3.3.4 SAMPLE TECHNIQUE (NASOPHARYNGEAL)

Figure 1 Oropharyngeal Swab

• Insert nasopharyngeal swab through the nares parallel to the pallet (not upwards) until resistance is encountered

• Gently rub and roll the swab and leave the swab in place for several seconds to absorb secretions before removing

• Withdraw slowly with a rotating motion


3.4 CHEST RADIOGRAPHYThe findings on Chest X-Ray are not specific, and in the initial phases of the disease the studies could be normal.

The most common features include lobar/ multi-lobar / bilateral lung consolidation

Multifocal consolidation in Right mid zone and left mid/lower zones

Perihilar and apical, mostly peripheral, opacification bilaterally

3.3.6 SAMPLE TRANSPORTATION• Label properly and to paste a sticker to identify the samples as COVID-2019 suspected• Specimens in viral transport media and other samples like blood, urine should be packed

in separate zip lock bags individually• All samples of the same patients should be packed in a big zip lock bag and sealed

properly• Samples should be transported by hand with proper documents (Request forms /case

reporting form for acute respiratory illness)• Transport in a cooler box with ice packs (if sent from another center other than IGMH).• If the package is transported by air, triple packaging as per WHO Guidelines for the safe

transport of infectious substances and diagnostic specimens as endorsed by IATA and ICAO should be followed.

• If there is any spillage during transport, follow spill decontamination procedure as mentioned in HPA guideline(1).

Figure 3 X-ray findings in patient with COVID-19 (A)

Source: Radiologyassistant.nl


Chest radiograph on admission demonstrates bilateral, almost symmetrical areas of peripheral consolidation with perihilar infiltrates and an indistinct left heart border

Table 1 Stages of CT findings

3.5 COMPUTED TOMOGRAPHYRecent studies have reported the features on CT imaging. It is recommended to minimize the use of CT given the challenges with isolation and transport. Decisions to do CT should be made on an individual basis depending on clinical judgment.

There are four stages of CT finding in COVID-19. Refer to Table 1 below for stages of CT Chest.

Early-stage Progressive Stage Peak Stage Absorption Stage

0-4 days after the onset of the symptoms



>14 days after the onset of the symptoms

Ground glass opacityGround glass opacity and consolidation in both lungs or multi-lobe distribution

Dense consolidation in both lungs or multi-lobe distribution

No Crazy pavingGround glass opacity might remain

Mostly seen in lower lobes

Residual parenchymal bands

Normal CT in some patients

Figure 4 X-ray findings in patient with COVID-19 (B)Source: Radiologyassistant.nl

Bilateral consolidation


CT Scan obtained on illness days 1 showed multiple pure ground-glass opacity mainly in right lower lobe.

shows reticular pattern in the subpleural areas of the bilateral lower lobe, GGO, and bronchial wall thickening (white arrow) in the right middle lobe

Scan obtained on illness days 8 showed small consolidation scattered in both lower lobes.

distinctive hazy patches on the outer edges of the lungs.

3.6 LUNG ULTRASONOGRAPHYThe ultrasonography findings are not specific for COVID-19 infection. However, it is a tool that could be used, if available, at the bedside for making a rapid diagnosis such as pleural effusion, consolidation, pneumothorax and pulmonary oedema while avoiding the need for shifting infected patients to a Radiology suite.

The common findings seen in COVID-19 include Irregular pleural lines, sub-pleural areas of consolidation, areas of White lung and thick B lines. Loss of usual sea-shore sign in M-mode with findings of Barcode sign and lung point could sensitively diagnose pneumothorax.

Figure 5 CT findings in patient with COVID-19

Source: Radiologyassistant.nl


Clinical Classification4

4.1 ASYMPTOMATIC

COVID-19 present in different syndromes including mild illness, pneumonia, severe pneumonia, acute respiratory distress syndrome, sepsis and septic shock(3). A significant number of patients with the disease can be asymptomatic.

Clinical features vary according to clinical syndrome; however, the most common presenting complaints are fever and cough, whereas nausea, vomiting and diarrhoea are uncommon(4,5). Patients with mild illness may have nonspecific symptoms such as anorexia, malaise, fatigue, muscle pain, sore throat, nasal congestion or headache(3).

Although the majority of the cases present as mild illness (46.1 - 80.9%), a significant number has severe disease (24.9 - 14%) and 5 % have critical disease with a disease fatality rate of 2.3 – 7.2 % (6,7)

Older age, presence of comorbidities, high Sequential Organ Failure Assessment (SOFA) score and d-dimer >1mcg/ml are considered to be risk factors for mortality.(5)

Any patient tested positive for COVID-19, who is asymptomatic, should be admitted to an isolation facility and monitored for the development of symptoms.

The patients should be isolated for 2 weeks and testing should be repeated at the end of the isolation period. If negative, repeat the test with another sample after 24 hours.

Consider discharge only after 2 consecutive samples result in negative after the isolation period.

Figure 6 Clinical Classification of COVID19

Asymptomatic COVID-19 patient

Isolate the patient for 2 weeks

Repeat the test at the end of the isolation period

If positive - repeat testingevery 72 hours

If negative- repeat testingevery 24 hours

Repeat test

Discharge after 2 consecutivesamplesare negative

Figure 7 Algorithm for asymptomatic patients


Table 2Supportive therapy for patients with mild uncomplicated illness.

4.2 MILD UNCOMPLICATED ILLNESS

Patients who have mild symptoms without high risk comorbidities are considered a mild uncomplicated illness. Refer to table 3 for a list of conditions considered as high risk.

The most common symptoms at the onset of illness were fever (98%), cough (76%), and myalgia or fatigue (44%). Sputum production was seen in 28% of the patients (8). These patients do not have warning signs such as shortness of breath or difficulty in breathing and hemoptysis. Some patients also presented with with hypogeusia or ageusia along with hyposmia or anosmia(9), gastrointestina symptoms (10) such as nausea, vomiting, and/or diarrhoea and without changes in mental status (i.e. confusion, lethargy). Few patients have been reported to have cutaneous manifestations such as erythematous rash, widespread urticarial and chickenpox-like vesicles (11).

4.2.1 MANAGEMENT OF MILD UNCOMPLICATED ILLNESS

4.2.2 DISCHARGE CRITERIA

All patients should be admitted to an Isolation Facility and patients should be assessed daily for clinical deterioration.

Special attention should be given to respiratory rate and SPO2 as these may be the initial signs of development of respiratory complications.

Initial investigations should include CBC with differential count & CRP.

All patients should receive supportive therapy as given in Table 2.

• Send RT-PCR, 72hrs after clinical recovery, at least 10 days after the first positive sample. If this sample is still positive, send a second sample after another 72hrs.

• Patients can be discharged from isolation facilities only after 2 negative samples of RT-PCR, 24 hours apart.

• Patients should be advised for home isolation for a total duration of 3 weeks from the onset of symptoms or 1 week after negative RT-RCR (whichever is longer).

Fexofenadine 180mg/120mg HS or Cetirizine 10mg HS or Levocetirizine 5mg HS or Loratadine 10mg HS

Paracetamol 500mg to 1 gm SOS / (Maximum 3gm/day for patients with normal liver functions; if impaired liver functions less than 2 gm/day)

Supportive Therapy

Antihistamines

Antipyretics

Adequate Hydration


4.3 MILD COMPLICATED ILLNESS

4.3.1 MANAGEMENT OF MILD COMPLICATED ILLNESS

Patients who have mild symptoms with high risk comorbidities are considered as mild complicated illness. Refer to table 3 for a list of conditions considered as high risk.

These patients are at high risk of developing severe disease and mortality hence needs to be closely monitored.

All patients should be admitted to an Isolation Facility and patients should be assessed daily for clinical deterioration, with special attention to sPO2.

Age > 60 years

Diabetes Mellitus

Hypertension

Chronic Kidney Disease

Severechroniclungdisease(e.g.bronchialasthma,COPD,cysticfibrosis,bronchiectasis,OSA/OHS,bronchopulmonarydysplasias,cerebralpalsywithrecurrentpneumonia,trachdependency etc…)

Heart disease

Immunocompromisingconditionsand/orpatientsonimmunospuressants(e.gprednisolone>20mg/day,chemotherapy,mycophenolate,cyclosporine,azathioprine,tacrolimus,TNFinhibitors,monoclonalantibodiesetc…)

Transfusiondependentthalassemias

Longtermcarefacilityorgrouphomesetting

Table 3list of conditions considered as high risk for patients with COVID-19

Table 4Investigations for patients with Mild complicated illness.

Recommended InvestigationsCBCwithdifferentialcount

CRP

GRBS

RFT

Sodium

LFTs

ECG 12 Leads

Chest Radiography (X-ray)


All patients should receive supportive therapy as for mild uncomplicated illness. (Refer to section 4.2.1 Management of mild uncomplicated illness).

Consider HCQ in patients with mild complicated illness. (Refer to Anex 1 for dose and Monitoring).

Inhaled medications should be given by metered-dose inhaler instead of nebulization as nebulization risks aerosolization of SARS-CoV-2. However, if nebulized medications are to be used used then precautionary measures should be taken and appropriate PPE should be used.

All patients who are already on ACE inhibitors for any reason may continue to use the drug unless clinically indicated (12).

Investigations

4.3.2 DISCHARGE CRITERIA

4.4.1 MANAGEMENT OF MILD PNEUMONIA

• Send RT-PCR, 72hrs after clinical recovery, at least 10 days after the first positive sample. If this sample is still positive, send a second sample only after another 72hrs.

• Patients can be discharged from isolation facilities only after 2 negative samples of RT-PCR, 24 hours apart.

• Patients should be advised for home isolation for a total duration of 3 weeks from the onset of symptoms or 1 week after negative RT-PCR (whichever is longer).

All patients should be admitted to an Isolation Facility and patients should be daily assessed for the development of severe pneumonia or ARDS. Clinical assessment should be done daily or as needed.

4.4 MILD PNEUMONIA

These are patients who present with pneumonia without any signs of severe pneumonia and requirement of supplemental oxygen. Refer to Section 4.4 for the definition of severe pneumonia.

CBC with differential countSodiumGRBSPotassiumLFTsRFTCRPECG 12 leadsChest radiography (Xray/CT)Troponin & CK-MB (if applicable)

• Investigations must be repeat every 3rd day: CBC with Differential count, CRP, other bloods tests if clinically indicated e. g. Renal function if renal impairment.

• If clinically worsening then send CBC with differential, Sodium, Potassium, LFTs, Troponin & CK-MB, LDH, CRP, ECG, Chest radiography (Xray/CT) and Magnesium, D-dimer, PTT/INR, Ferritin, ABG where available

LDH D-dimerFerritinLactateABGPTT/INRSputum C/S + Gram StainInfluenza screeningMagnesium

RecommendedInvestigations Investigations (Where available)

Table 5 Recommended

investigations for Mild Pneumonia


4.4.1.1 EMPIRIC ANTIBIOTICS

4.4.1.2 ANTI-VIRAL AND ANTI-INFLAMMATORY

• Ceftriaxone 1g BD – for 5-7 days + Azithromycin 500mg OD – 3 to 5 days.

• If penicillin allergy, use Inj. Levofloxacin 750mg OD – 5 to 7 days

• Renal dose adjustment:

• Creatinine clearance 20 – 49 ml/min reduce dose to 750mg every 48 hours.

• Creatinine clearance 10 – 19 ml/min reduce dose to 750mg STAT then 500mg every 48 hours.

• Patients on Haemodialysis of CAPD reduce dose to 750mg STAT then 500mg every 48 hours.

• If the patient is known to have chronic lung disease then an antibiotic with anti-pseudomonal coverage like Ceftazidime, Cefepime or Piperacillin/Tazobactam should be used.

• Oseltamivir 75mg BID x 5 days for adult patients with normal renal function (stop oseltamivir if Influenza PCR negative)

• Renal dose adjustment of Oseltamivir:

• Creatinine clearance 30 – 60 ml/min reduce dose to 30mg BD

• Creatinine clearance 10 – 30 ml/min reduce dose to 30mg OD

• Creatinine clearance < 10 ml/min not on HD – Not recommended

• Patients on HD – 30mg STAT and after each HD session.

• Consider HCQ. Refer annexe 1 for dosage and monitoring of HCQ.

4.4.2 DISCHARGE CRITERIA• Send RT-PCR, 72hrs after clinical recovery, at least 10 days after the first positive

sample. If this sample is still positive, send a second sample only after another 72hrs. • Patients can be discharged from isolation facilities only after 2 negative samples of

RT-PCR, 24 hours apart.• Patients should be advised for home isolation for a total duration of 4 weeks from the

onset of sympt oms or 2 weeks after negative RT-PCR (whichever is longer).


4.5 SEVERE PNEUMONIA

Adolescent or adult: Fever or suspected respiratory infection, and any one of the following:• Respiratory rate >30 breaths/min• Severe respiratory distress• SpO2 ≤ 93% on room air.

4.5.1 MANAGEMENT OF SEVERE PNEUMONIA

4.5.1.1 OXYGEN THERAPY

All patients should be admitted to an Isolation Facility with Intensive care and should be assessed for worsening of the condition.Clinical assessment should be done twice daily or as needed.

Nasal Cannula covered by a surgical mask can be used: Use humidified nasal cannula 1 to 5 LPM and target SpO2 should be between 92-96%.

Venturi Masks are recommended if the patient requires > 5 LPM via nasal cannula. (Refer to table Table 4 in the next page).• Initiate dry Venturi mask (non-humidified) to reduce aerosolization risk.• Up-titrate FiO2 to goal SPO2 of 92 – 96%

Investigations

CBC with differential countSodiumPotassiumGRBSLFTsRFTCRPECG 12 leadsChest radiography (Xray/CT)Troponin & CK-MB (if applicable)

• Investigations must be repeated every other day: CBC with Differential count, CRP, other bloods parameters if clinically indicated e. g. Renal function if renal impairment.


LDH CalciumMagnesiumLactateD-dimerFerritinABGPTT/INRBlood C/SSputum C/S + Gram StainInfluenza screening


Table 6Recommended investigations for Severe Pneumonia


Oxygen Delivery Devices

Device Flow Rate % Oxygen Delivered

1 L/min 24%

Nasal Cannula 2L/min 28%

4 L/min 36%

Blue 2 - 4 L/min 24%

White 4 - 6 L/min 28%

Venturi valve & Mask Yellow 8 - 10 L/min 35%

Red 10 - 12 L/min 40%

Green 12 - 15L/min 60%

Non-Rebreather Mask 15 L/min 85%

Table 7Oxygen delivery devices

• Noninvasive Ventilation:

• NIPPV is used for patients who fail to achieve target SPO2 of 92 – 96% with Venturi 60%

• Recommended NIPPV Settings:

• Mode: CPAP

• Pressure: 10 cm H20

• If NIPPV is used, it must be under strict airborne precautions ideally in a negative pressure room

• Trial of NIPPV can be given for one hour

• For patients on NIPPV, the transition to Venturi mask or non-rebreather mask (where possible) are recommended to be done 45 minutes before intubation.

• Monitor closely, at least every 15mins for worsening of respiratory status and intubate early if worsening occurs.

• Trial of awake proning can be considered before intubation (Refer to Annexe 2 for Awake proning protocol).

• Intubation: (Refer to section 6 Intubation)

• Patients who are not able to achieve the target SPO2 92 – 96% with NIPPV after 1 hour, should be considered for intubation


Table 8Suggested antibiotic regimens for severe Pneumonia

4.5.1.2 FLUID MANAGEMENT

4.5.1.3 EMPIRIC ANTIBIOTICS

4.5.1.4 ANTIVIRAL AND IMMUNE-MODULATING THERAPIES

• Fluid management should be conservative due to the risk of hypoxia/CHF.• Oral hydration is preferred to Intravenous hydration if the patient can take orally.• It is advised to maintain a negative fluid balance of 0.5 – 1L/day.

• Clinical reports indicate that rates of bacterial superinfection of COVID19 are low (10-20%), but when present increase mortality risk. Unnecessary antibiotics carry risks of fluid overload and drug-resistance. Moreover, there is the possibility that antibiotics may become a limited resource (13).

• Refer to table 6 for suggested antibiotic regimens for severe Pneumonia.

• Consider HCQ in all patients with severe pneumonia. Refer Annexe 1 for dosage and monitoring of HCQ.

• Refer Annexe 1 for dosage and monitoring of HCQ and other experimental drugs used in COVID-19 treatment.

• For coverage of potential coinfections:• If concurrent influenza, treat with oseltamivir 75mg BD (dose should be

adjusted according to eGFR)• Give oral antibiotics (azithromycin, levofloxacin, ciprofloxacin, etc.) when

possible to reduce volume load, unless concerns for poor oral absorption.• Antibiotics should be de-escalated as per culture sensitivity and should be

discontinued as soon as clinical improvement is achieved.• Clinical judgement should prevail over any specific lab value.

• > 48 hours after hospital admission

• Patients residing in long term health

care facility

• Patients undergoing dialysis

• Duration – 7 to 10 days

• Intravenous antibiotic treatment during

the prior 90 days

• Prior detection of MRSA.

Inj. Augmentin 1.2gm BD or Inj. Ceftriaxone 2gm ODPLUSTab. Azithromycin 500mg OD

ADD Vancomycin 15 mg/kg IV q8-12h (consider a loading dose of 25–30 mg/kg × 1 for severe illness)ORIV/PO Linezolid 600 mg q12h

Inj. Piperacillin/ Tazobactum 4.5gm QIDORInj. Ceftazidime 2gm TDSORIV/PO Levofloxacin 750 mg OD / Inj. Ciprofloxacin 400 mg IV TDSORInj. Meropenem 1gm TDS

CommunityAcquiredpneumonia

If higher risk for MRSA

Healthcareassociatedpneumonia





onset of symptoms or 2 weeks after negative RT-PCR (whichever is longer).

4.6 ACUTE RESPIRATORY DISTRESS SYNDROME

Many patients with COVID-19 who require ICU level of care, will develop ARDS. Anecdotally, many reports that progression of hypoxemic respiratory failure occurs rapidly (within ~12-24 hours). The median time from onset of symptoms to ARDS was 9·0 days (8·0–14·0), to mechanical ventilation was 10·5 days (7·0–14·0) (8).

When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including in non-ventilated patients)

The Berlin definition of ARDS requires the following four criteria:1. Onset:neworworseningrespiratorysymptomswithinoneweekofknownclinical

insult

2.Chestimaging(radiograph,CTscan,orlungultrasound):bilateralopacities,not

fullyexplainedbyeffusions,lobarorlungcollapse,orlungnodules

3.Mustnotbefullyexplainedbycardiacfailureorfluidoverload

4.PFratio<300mmHgwithaminimumof5cmH20PEEP(orCPAP)

Severity PaO2/FiO2 (on PEEP/CPAP >5)

Mild 200 - 300

Moderate 100 - 200

Severe < 100 Table 9Severity of ARDS

4.6.1 MANAGEMENT OF ARDSAll patients should be admitted to an Isolation Facility with Intensive care and should be assessed for deterioration of the clinical condition.

Patients with ARDS should be monitored more frequently.

Daily investigations can be done (CBC with Differential count, CRP, other bloods parameters if clinically indicated eg Renal function if renal impairment.)


Investigations

CBC with differential countSodiumPotassiumGRBSLFTsRFTCRPECG 12 leadsChest radiography (X-ray/CT)Troponin & CK-MB (if applicable)

• Investigations must be repeated daily: CBC with Differential count, CRP, other blood parameters if clinically indicated e. g. Renal function if renal impairment.


LDH MagnesiumCalciumLactateD-dimerFerritinABGPTT/INRBlood C/SSputum C/S + Gram StainInfluenza screening


Table 10Recommended

investigations for ARDS

General Measures Venilator Settings Monitor Parameters Adjunct Measures

Nutrition support: NG feeds: early full-calorie enteral nutrition.

Stress Ulcer prophylaxis

Inj. Ranitidine 50mg BD

DVT prophylaxis

Inj. LMWH 40mg S/C OD

Mode : Volume Controlled

Tidal Volume: low tidal volume ventilation (4-6 mL/kg of predicted body weight) : Refer to Annexe 3 for predicted body weight chart.

Use a higher positive end-expiratory pressure strategy (PEEP ≥ 10)

Adjust the PEEP to maintain the SpO2 within 88-95%

After changes have been completed, check the plateau pressure (Pplat). Target plateau pressures of <30 cm H2O

If the Pplat is >30 cm H2O and driving pressure (Pplat minus PEEP) is >15 cm H2O, decrease the Vt by 1ml/kg increments until the Pplat is less than or equal to 30 cm H2O or driving pressure <15 cm H2O (minimum Vt = 4 ml/kg).

Arterial pH: 7.30- 7.45 (may allow as low as 7.15): Allow permissive hypercapnia

Oxygen saturation 88 - 95 %

PaO2 : 55-80 mmHg

Plateau pressure: <30 cm H2O

Conservative fluid therapy – Aim for a negative balance of 0.5

to 1 litre per day. (14)

Antibiotics as per section on severe pneumonia

Inj.Methylprednisolone at 1–2 mg/kg/day for 5–7 days was associated with a shorter duration of supplemental oxygen use.

Consider HCQ in all patients with ARDS (Refer to Annexe 1 for regimen)


General Measures

Moderate to severe ARDS For adults receiving mechanical ventilation who have moderate to severe ARDS, prone ventilation for 12 to 16 hours

Use as-needed neuromuscular blocking agents (NMBAs) instead of continuous NMBA (Inj Atracurium 0.5mg/kg bolus)

Table 11Summary of management of ARDS

4.6.1.1 PRONE POSITIONING• Prone Position (PP) ventilation can be considered for patients with moderate

to severe ARDS (PaO2/FiO2 < 150, FiO2 > 0.6) for 12 – 16 hours / day.

• However, PP ventilation is labour-intensive and involves more staff exposure.

• The patient may require bolus doses of neuromuscular blockade (Inj Atracurium 0.5mg/kg). Avoid giving continuous infusion.

• Be vigilant of development of pressure sores and mechanical complications such as ET tube dislodgment.

• Monitor the patient every 5-15 minutes for progress, if patient’s health is deteriorating hemodynamically turn supine position.

• Discontinue proning when oxygenation has improved (Pao2/FIO2 > 150 with a PEEP <10 cm H2O, FIO2 > 0 .6 ) for at least 4 hours in the supine position.




onset of symptoms or 2 weeks after negative RT-PCR (whichever is longer).


4.7 SEPSIS & SEPTIC SHOCK

The prevalence of shock in patients with COVID-19 has been highly variable from 1% to 35% (4, 15). Shock is the most common cause of death in patients (40%) with COVID-19 (16). Some of the risk factors associated with the development of shock are old age, comorbidities (diabetes, cardiovascular diseases, hypertension), lower lymphocyte count, elevated D-dimer (17).

4.7.1 DIAGNOSIS OF SEPSIS AND SEPTIC SHOCKThe qSOFA (quick sepsis related organ failure assessment) score is a validated ICU mortality prediction score, to help identify patients with a suspected infection that are at higher risk for poor outcome. (Refer to Table 12).

Septic shock is when a patient requires vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg and Lactate is ≥ 2 mmol/L, in the absence of hypovolemia.

In centers where lactate levels are not available, MAP and clinical signs of perfusion can be used to recognize shock. (Refer to tables 13 and 14).

Respiratory rate > 22 breaths / minSystolic blood pressure < 100 mmHgAltered mental status: GCS < 15

Each parameter will be given 1 point if present

Systolic blood pressure + (2 x Diastolic Blood pressure)

3

A “positive” qSOFA Score (≥2) suggests a high risk of poor outcome

qSOFA SCORE

Mean Arterial PressureTable 12qSOFA Score

Table 14Clinical features of compensated and decompensated shock

Table 13Mean Arterial Pressure

Parameter Normal Compensated Shock Shock

Conscious level Clear and Lucid Clear and Lucid Restless and combative

Capillaryrefilltime Brisk (<2s) Prolonged (>2s)Very prolonged and Mottled skin

Extremities(Colour/Temp) Warm and Pink Cool peripheries Cold and Clammy

Peripheralpulsevolume Good volume Weak and thread Feeble or absent

Heart rate Normal for age Tachycardia for ageTachycardia or Bradycardia in late stage.

Blood pressure Normal for ageNormal SBP but raising DBPPostural Hypotension

Hypotension and unrecordable BP

Pulse Pressure (SBP - DBP)

Normal for ageNarrow pulse pressure (<20 mmHg)

Narrow pulse pressure (<20 mmHg)

Respiratory rate Normal for age Quiet Tachypnea Kussmaul’s breathing

Urine Output Normal Reducing tend Oliguria/Anuria


4.7.2 MANAGEMENT OF PATIENTS WITH SEPSIS AND SEPTIC SHOCK

4.7.2.1 INITIAL RESUSCITATION

The treatment of sepsis and septic shock should begin immediately after recognition. When giving intravenous fluids, care must be taken to give a conservative amount of fluids.

Adults: Intravenous fluids (Normal saline/Ringer’s lactate) 250-300 ml rapid boluses given in the first 15 – 30 mins. Reassess the patient after each bolus by checking patients’ blood pressure and other signs of perfusion.

The purpose of intravenous fluids is to achieve the targets mentioned in Table 15.

Excessive fluid administration may lead to volume overload resulting in respiratory failure especially with ARDS. Therefore, when managing patients with IV fluids, observe for signs of volume overload mentioned in Table 16.

If any of these signs are present, reduce or stop IV fluids, especially in patients with hypoxemic respiratory failure

Mean arterial pressure > 65 mmHg or age-appropriate targets in children

Urine Output > 0.5ml/kg/hr in adults, 1ml/kg/hr in children

Improvement of skin mottling and extremity perfusion

Capillary refill < 2 s

Heat rate reduction trend

Level of consciousness improvement

Lactate reducing trend

Jugular venous distension

Crackles on lung auscultation

Pulmonary edema on imaging

Hepatomegaly in children

PERFUSION TARGETS TO ASSESS AFTER EACH FLUID BOLUS

SIGNS OF VOLUME OVERLOAD

Table 15Perfusion targets to assess after each fluid bolus

Table 16Signs of volume overload


4.7.2.2 VASOACTIVE AGENTS

4.7.2.3 CORTICOSTEROIDS

Norepinephrine is the first-line drug recommended for septic shock. In centers where Norepinephine is not available Epinephrine can be used as an alternative first-line agent.

Patients with evidence of cardiac dysfunction and persistent hypoperfusion despite fluid resuscitation and norepinephrine, we suggest adding dobutamine, over increasing norepinephrine dose is suggested.

It is recommended to target a MAP of 60–65mmHg, rather than higher MAP targets.

Norepinephrine and Epinephrine:• Preparation: 4 mg in 50 ml NS or 8 mg in 100 ml NS• Dose: 0.01- 0.3 mcg/kg/min • Route: Central line recommended (Most Distal Port)• Dose chart (Table 17) can be used which gives ml/hr. based on body weight

as shown in the table below (Dose on x-axis and body weight on y-axis)• Adjust the weight to the nearest number

There is no role of routine use of corticosteroids in patients with COIVD-19. However, for patients with refractory shock, it is recommended to use low dose corticosteroid therapy (“shock reversal”).

• Inj. Hydrocortisone 50mg QID

Dopamine and Dobutamine:• Preparation: Body weight x 3 in 50 ml in NS• Preparation: Body weight x 6 in 100 ml NS• ml/hr = mcg/kg/min; E.g. 5 ml/hr = 5 mcg/kg/min• Dose: 5 - 20 mcg/kg/min• ONLY USE in Dosage: 5/7.5/10/15/20 mcg/kg/min• Route: Peripheral/ Central line (Most Distal Port)

Table 17Dose chart of Norepinephrine and Epinephrine

mcg/kg/minWeight (Kg) 0.01 0.02 0.05 0.1 0.15 0.2 0.3

30 0.25 0.5 1.2 2.5 3.8 5 7.5

40 0.3 0.6 1.5 3 4.5 6 9

50 0.4 0.8 2 4 6 8 12

60 0.5 1 2.5 5 7.5 10 15

70 0.55 1.1 2.8 5.5 8 11 16

80 0.6 1.2 3 6 9 12 18

90 0.7 1.4 3.5 7 10.5 14 21

100 0.8 1.6 4 8 12 16 24


4.7.2.4 ANTIBIOTICSAll patients with sepsis or septic shock should receive a broad-spectrum antibiotic. It should be given within 1 hour of recognition of sepsis/septic shock(17).

It is recommended to use one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (bacterial, potentially fungal or viral) (17).

Relevant cultures (including blood culture) should be taken ideally before administration of antibiotics. However, this should not delay the administration of antibiotics. Blood cultures require at least 10ml of blood and two sets of blood cultures (Aerobic and Anaerobic).

It is recommended to start empiric combination therapy (using at least two antibiotics of different antimicrobial classes) aimed at the most likely bacterial pathogen(s) for the initial management of septic shock. Combination therapy connotes the use of two different classes of antibiotics (usually a β-lactam with a fluoroquinolone, aminoglycoside, or macrolide) (17). See Table 19 for suggested antimicrobial regimens.

The addition of a supplemental gram-negative agent and MRSA coverage to the empiric regimen is recommended for critically ill septic patients at high risk of infection with such multidrug-resistant (MDR) pathogens (e. g. Pseudomonas, Acinetobacter, etc.) to increase the probability of at least one active agent being administered. See risk of multidrug-resistant pathogens in Table 18.

History of infection with MDR pathogen

Recent use of Antibiotics (< 3months)

Recent hospitalizations (< 3months)

Dialysis

Indwelling devices

Structural lung disease/bronchiectasis, COPD (Pseudomonas)

Wounds

Dental plaque

RISK FACTORS FOR MULTIDRUG-RESISTANT PATHOGENS

Table 18Risk factors for MDR pathogens (18)

Antibiotics regimen should be deescalated after the culture sensitivity reports.

Antimicrobial therapy of 7 -10 days is sufficient for most cases with sepsis/septic shock (17).


Table 19Suggested Antibiotics for sepsis/septic shock

• Intravenous antibiotic treatment during

the prior 90 days

• Prior detection of MRSA.

Inj. Piperacillin/ Tazobactum 4.5gm QID ORInj. Ceftazidime 2gm TDS ORIV/PO Levofloxacin 750 mg OD ; IV/PO Ciprofloxacin 400 mg IV TDSORInj. Meropenem 1gm TDS(renal dose adjustment required)

ADD Vancomycin 15 mg/kg IV q8-12h (consider a loading dose of 25–30 mg/kg × 1 for severe illness)ORIV/PO Linezolid 600 mg q12h

Suggested Antibiotics for Sepsis / Septic Shock

If the higher risk for MRSA


Complications of COVID-1955.1 ACUTE KIDNEY INJURY

5.2 LIVER DERANGEMENTS IN COVID-19

AKI has been reported in 25 to 29% of patients with critically ill(19).

The most likely cause of AKI in these patients is Acute Tubular necrosis due to shock.

Monitor• Daily Creatinine• Urinary output and Input: depending on clinical condition frequency might be from 8hrly to

hourly• Urine RE for Hematuria and Proteinuria• ABG might be needed to detect metabolic acidosis• Random urinary sodium (if available)

Management

Minimize nephrotoxic agents

eGFR should be measured and ALL medications should be adjusted according to eGFR

Avoid fluid overload and adjust IV fluids accordingly, especially when managing shock.

Indications for Dialysis are same as for any other patient.• Refractory fluid overload• Severe Hyperkalemia (K+ > 6.5mEq/L) – not responding to treatment or rapidly increasing K+.• Signs of uremia – Pericarditis or Encephalopathy• Severe metabolic acidosis (pH < 7)

Options of Dialysis:• Continuous renal replacement therapy (CRRT) is preferred among critically ill if available

especially if the patient is in shock with low BP• Intermittent Hemodialysis: would be difficult in a patient in shock with low BP• Intermittent PD can be used where applicable, and if available

Prognosis: Increased Creatinine, Urea, AKI, Proteinuria or hematuria are each independent risk factors for In-Hospital death.

COVID-19 has been reported to cause increased liver biochemistries in 15-53% of patients (20,21). The profile of the liver biochemistry abnormalities is most commonly an elevation of the aminotransferases (AST and ALT), with occasional alkaline phosphatase and total bilirubin elevations. The severity of liver derangement tends to correlate with disease severity (20-22). Careful monitoring is also needed to identify the occurrence of liver injury due to the usage of drugs, such as antibiotics, steroids and antivirals, which may be used for the treatment of COVID-19.


5.3 NEUROLOGICAL COMPLICATIONS

5.4 HEMATOLOGICAL COMPLICATION

Neurologic manifestations are being reported increasingly in recent case studies of COVID-19. More than third (36.4%) of 214 COVID-19 in-patients in a Wuhan hospital exhibited neurological signs and/or symptoms during the infection. The most common neurologic symptoms were dizziness (16.8%), headache (13.1%), impaired consciousness (7.5%), hypogeusia (5.6%), hyposmia (5.1%) (23).

Ischemic stroke (5%) was reported more commonly than intracerebral hemorrhage (0.5%) or cerebral venous sinus thrombosis (0.5%). Stroke was seen to be more common in “severe” COVID-19 presentations (24). Therefore, standard clinical management for stroke should be followed in COVID-19 patients.

Observational series from Italy suggests Guillain–Barré syndrome could be associated with COIVD-19 and it should be considered in patients who develop early respiratory failure in the absence of typical ARDS picture or patients who fails weaning off from ventilator despite recovery from ARDS (25).

Recent case series reports suggest there may be increased venous thromboembolism (VTE) in COVID-19 patients, though the incidences are not clear (26). Colleagues from Wuhan and Italy have reported finding microthrombi in pulmonary vasculature on autopsy, which could contribute to local V/Q mismatch or hydrostatic changes causing edema (27). DIVC has also been reported in COIVD-19 patients, with increased incidence with the severity of disease.

VTE Prevention: COVID-19 patients with respiratory failure or comorbidities, such as cancer or heart failure and obesity should receive pharmacological prophylaxis unless contraindicated. If pharmacological prophylaxis is contraindicated, mechanical VTE prophylaxis (intermittent pneumatic compression) should be considered in immobilized patients. Regime for VTE prophylaxis: Subcutaneous Clexane 0.4mg OD (half the dose if eeGFR <30) (28). UFH 5000u BD is an option where Clexane is not available.

For the management of DIC, consider blood products (FFP or Platelets) for patients with bleeding manifestation as appropriate and withhold any anticoagulation.

Recommendations for evaluation of abnormal LFTs in a person presenting with suspected or confirmed COVID-19.

• Avoid testing for HBV/HCV viral load (PCR) unless there is an identifiable risk factor or needed for a COVID-19 treatment protocol with immunomodulators.

• Avoid Ultrasound unless there is a concern for biliary obstruction, cholangitis, or venous thrombosis

• Consider DILI (macrolides or quinolone, steroids, Lopinavir/ritonavir, antifungal) as a cause of LFT elevations

• Monitor the LFT trend daily and consult Physicians for LFTs over 5 times the upper limit of the normal or rapid rise


5.5 CARDIAC COMPLICATIONSCardiac complications are common in COVID-19 patients and are often associated with high mortality. Cardiac complications reported include arrhythmias, acute cardiac injury, pericarditis, myocarditis, heart failure and pericardial effusion (29). Acute cardiac injury is defined as troponin raise more than 99th percentile upper limit of normal, while earlier studies also included abnormal ECG or echocardiographic evidence. Troponin and BNP elevations are seen commonly in COVID-19 and signify toxic myocardial injury and is associated with high mortality (30).

Recommendations in management of cardiac complications.

• Troponin and BNP: Should only be done if the diagnosis of acute MI or heart failure are being considered on clinical grounds. An abnormal result should not be considered as evidence for an acute MI or heart failure without corroborating evidence (30,31).

• POCUS Echo: Can be used, depending on availability, to assess patients with features of heart failure, significantly raised troponin, and/or ECG changes.

• Formal Echo assessment: Should be restricted to patients with evidence of myocardial injury or when abnormalities detected on POCUS Echo. Should only be requested for those patients in whom these procedures are expected to bring a meaningful change in management and outcome (31).

• Acute Coronary Syndrome: Based on the currently available data and recommendations of various cardiac societies, an initial conservative strategy consisting of early fibrinolysis is recommended for low-risk STEMI. For NSTEMI, medical management with anticoagulation is recommended. Invasive management should be reserved for refractory angina, hemodynamic or electrical compromise attributed to myocardial ischemia (32). Consult the cardiology team for guidance when required.

• Atrial Fibrillation: use Beta-blockers (e. g. Metoprolol 25mg BD /Carvedilol 3.125mg BD) if no evidence of acute heart failure or shock. If significant heart failure or borderline BP, use amiodarone *(150mg IV over 10mins then 1mg/min for 6hours then 0.5mg/min over 1hour). If hemodynamic instability is attributed to Fast AF, cardiovert with Synchronized 200J. *use with caution if liver functions are significantly deranged.

• Pericarditis and Myocarditis: Treat with direct viral treatment and supportive therapy for heart failure if present. Use of steroid, colchicine and NSAIDs should be considered only after consultation with cardiology team.


5.6 CARDIAC ARRESTAll patients arriving in cardiac arrest should be assumed as high risk for COVID-19 until it can be proven otherwise. Full PPE is recommended.

Standard ACLS algorithms should be followed (Refer to Figure8 for ACLS cardiac arrest algorithm).

As CPR is aerosol producing, chest compressions should not continue during the intubation attempt and intubation is greatly preferred over any other option.

Before initiating CPR and intubating consider the probability of survival and quality of lifepost-ROSC.Enquireaboutapriordiscussionregardingresuscitationandmechanicalventilation.

Atpresent it is feltthatmortality ishighest inelderlypatientsandthosewithunderlyingmedicalco-morbidconditions.Forcriticallyillpatients,COVID-19mayindicateaprognosisworse than thealreadypoorestimatedsurvivalofCPR incritically ill patientsoverall. Itisessentialtosharewithpatientsandfamiliesasaccurateaprognosisaspossible.Iftheclinicalassessmentisthat,attemptsatresuscitationareexpectedtobeharmful,ineffectiveorofnomedicalbenefitthisshouldbecompassionatelyconveyedtopatientsandfamilies.


Figure 8ACLS Cardiac Arrest AlgorithmAdapted from American Heart Association

VF / pVT


Intubation(33)6Intubation is an aerosol generating high risk procedure. The health care worker should wear appropriate personal protective equipment (N95 respirator, eye protection [goggles and visor], gloves and a gown). The number of HCW should be limited to three persons inside (one intubator; one assistant for bagging and cricoid pressure; and one to administer drugs and monitor the patient) and one runner outside the intubating room.

Know and communicate the plan before entering the room. Use a checklist and the algorithm or the cognitive aid planned to use in the room. Use clear language and close loop communication.

Prepare airway equipment and drugs outside the room as much as possible. Use a dump kit mat. The following equipment’s in Figure 10 can be used as per availability.

A direct laryngoscope / video laryngoscope

Oropharyngeal airways x 2

Stylet

Bougie

Endotracheal tubes (2 sizes)

Second generation supraglottic airway devices

Yankeuer suction tip

Tube fixation and lubrication

Bag, Mask and Valve device

Tube Clamp

Emergency FONA (front of neck access) kit

Syringe 10cc

• The most experienced airway manager should manage the airway.

• Be Safe, Accurate and Swift with the aim to succeed endotracheal intubation in the first attempt.

• Preoxygenation with well-fitting mask and a bag fitted with an HME filter for 3-5 minutes

Figure 9Suggested arrangement of resuscitation room

Figure 10Emergency tracheal intubation kit

Emergency Tracheal Intubation Kit


• Do not face-mask-ventilate unless needed. Use 2-person, 2-handed mask ventilation with VE grip for bag and mask ventilation and use low flow, low pressure if needed.

• Monitoring should include heart rate, blood pressure, oxygen saturation, continuous ECG tracing and waveform capnography if available.

• Use Rapid Sequence Intubation (RSI) technique for intubation with cricoid pressure (taken off if it causes difficulty).

• Drugs to be used arel listed in table 20.

• Ensure full neuromuscular blockade before attempting intubation.

• Vesopressor boluses (Adrenaline 100mcg [1ml of Adrenaline 1: 10 000]) or infusion should be available during the procedure to manage hypotensive episodes.

• Intubate with endotracheal tubes (with subglottic suction ports whenever available) of sizes 7.0-7.5mm (ID) for women and 7.5-8.0 mm (ID) for men.

• Pass the cuff 1-2 cm below the vocal cords. Inflate the endotracheal tube cuff before starting ventilation.

• Confirmation of the position of the tube is difficult while in PPE. Rely on bilateral chest rise and fogging of the ETT.

• Use a standard “failed tracheal intubation” algorithm with a cognitive aid if difficulty arises. Difficult airway algorithms should be discussed and displayed in the intubation room.

• Strictly avoid circuit disconnection. Use a tube clamp and pause the ventilator for airway manoeuvres or disconnections.

• Place a nasogastric tube after tracheal intubation.

• Consider taking Endotracheal sample after intubation, if closed suctioning is available.

• Meticulous doffing protocols and disinfection protocols should be followed

• Refer to Annexe 5 for Emergency endotracheal intubation checklist and Algorithm for intubation.

Table 20Drugs used in Rapid sequence intubation

Figure 11Face mask ventilation

Ketamine1-2mg/kg

Suxamethonium1.5mg/kg(ifnocontraindication)

Vecuronium0.3mg/kg(incaseofabsolutecontraindicationtosuxamethonium)


6.1 SEDATIONTarget RASS score of -2 to -3. (Refer to Annexe 5)If synchronous, target for a light sedation of RASS score 0 to -1.If the patient remains dyssynchronous despite sedation, change target RASS score of -4 to -5

Consider a multimodal approach in sedating intubated patients with COVID-19.

Refer to table 21 and 22 for list and doses of recommended opioids and sedatives.

Opioids

Sedatives

Inj Fentanyl @ 0.5mcg/kg x IV bolus and infusion @ 0.5-1.0 mcg/kg/hr

(Dilute 3 amplules 300mcg in 24ml NS in a 50ml syringe)

Inj Dexmedotomidine @ 0.5mcg/kg x IV bolus, and infusion @ 0.2- 1 mcg/kg/hr for 24 hours

OR

Inj Propofol @ 0.025-0.2mg/kg/min IV infusion.* Propofol is preferred in renal and liver dysfunction, ARDS* Use with caution in prolonged sedation, obesity, bradycardia* Monitoring: Triglycerides, CK and Lipase (if triglycerides elevated > 400) every 24-48 hours* If Triglycerides > 500, consider dose-reducing strategies prior to discontinuation (unless concern for pancreatitis)* If Triglycerides > 1000 or signs of pancreatitis, discontinue

Inj Morphine @ 0.1mg/kg bolus x IV and infusion @ 0.07-0.1mg/kg/hr,

If SC/ IM injections 5mg x 6th hourly. (use with caution in renal impairment and hemodynamic instability).

Inj Midazolam @ 1-2mg/hr infusion

*Preferred if propofol is contraindicated or as an adjunctive agent in neuromuscular blockade if needed.*Use with caution due to accumulation in obesity, renal dysfunction, liver dysfunction

Lorazepam 50mcg/kg x PNG (not more than 4mg) or 0.03-0.05mcg/kg x IM

Diazepam 0.03-0.1mg/kg IV bolus q30minutes- 6th hourly.

First Line

First Line

Second Line

Second Line

Figure 21Summary of first and second line drugs of opioids

Figure 22Summary of first and second-line drugs of sedatives


6.2 WEANING OFF VENTILATORClinical goal is to liberate patients from mechanical ventilation as soon as safe and feasible.All patients with the following parameter should be considered for extubation:

• Improving or stable respiratory disease• FiO2 ≤ 50%, PEEP ≤ 10 with SpO2 >92%• Hemodynamically stable (minimal to no vasopressor requirements to maintain target MAPs)

All patients should be assessed daily for readiness for weaning. Perform a daily spontaneous awakening trial (SAT), consisting of temporary cessation of sedatives until a RASS of 0 is achieved.Continuous paralytics discontinued for a minimum of 6 hours prior to SAT.

Hemodynamically stable is defined as HR < 120, MAP > 65, with minimal or no vasopressor support. SpO2 > 92% or PaO2 > 75 with an FiO2 ≤ 50% and PEEP ≤ 10 (and most recent Ppl < 30)

A daily spontaneous breathing trial (SBT) is considered for all patients who meet the requirements for a daily SAT

SBT consists of Pressure Support ventilation mode with a PS = 5 and PEEP = 5

• SBT discontinued if the patient develops• Evidence of increased work of breathing with RR > 30• Hypoxia (SpO2 < 92%)• Hemodynamic instability• Rapid shallow breathing index (RSBI) = RR/TV (in Litres) > 105

Terminate all SBTs after 30 minutes and return to prior VC settings if patients are deemed not ready to extubate.

Alternative agents:1. Ketamine @ 0.5mg/kg IV bolus and infusion

2. Acetaminophen 15mg/kg x IV QID

3. Xylocard @ 1mg/kg x IV bolus and infusion

Consider neuromuscular blockade, if the patient remains dyssynchronous despite sedation.

Inj. Atracurium 0.5mg/kg IV Bolus, and Infusion 0.25 – 0.5 mg/kg/hr

OR

Inj. Vecuronium 0.1 mg/kg IV Bolus, and Infusion 0.1mg/kg/hr

NeuromuscularBlockers

Table 23Neuromuscular blockers


Note: For patients who has unexplained respiratory fatigue and difficulty weaning off despite of improvement of other parameters, consider neurological complications such as GBS or new onset stroke.

Breathing Spontaneuously

RASS 0 to – 1

Able to follow commands

Intact cough and able to protect airway

Requiring airway suctioning for secretion < q2h

Other considerations include:

• FiO2 < 40% at the time of extubation

• Optimization of volume status prior to extubation

Place NG tube prior to extubation for patients intubated for >48h

EXTUBATION CRITERIA

Table 24Extubation criteria

6.2.1 PROTOCOL FOR EXTUBATION IN ICU• Don appropriate PPE.

• Only respiratory therapist and/or airway provider(anesthesiologist/intensivist) should be in the room.

• Confirm patient will tolerate extubation.

• Place patient on 1.0 FiO2 and ensure non-rebreather mask ready with flow “OFF”

• Place a towel on the patient chest and ensure yankauer suction on ready readily available

• Respiratory therapist to cut tape holding ETT, turn vent flows to “OFF” and extubate the patient

• Immediately discard of ETT and towel and immediately place non-rebreather, then turn oxygen flow to 10-15L/min

• Ensure patient is oxygenating and ventilating

• All providers will sanitize/change gloves while maintaining base layer PPE.


Figure 12Algorithm for Extubation

Adapted from Brigham and Women’s Hospital COVID-19 clinical guidelines


Special Consideration in Management of COVID 19

7

7.1 GERIATRIC AGE GROUP

7.2 PATIENTS WITH MULTIPLE COMORBIDITIES

7.2.1 PATIENTS WITH CARDIOVASCULAR DISEASES

Geriatric population (age > 65 years) is at increased risk of mortality due to COVID-19. Morbidity and mortality were noted to increase significantly with age – rising to 8%. among patients of 70-79 years of age and 14.8% in patients over 80 years of age in a large-scale Chinese case reporting (34). This category of patients not only have an array of multiple medical conditions, but also they are more likely to be survivors of cancers and/or on long term chemotherapeutic agents and immunosuppressive agents. They also often have undiagnosed medical conditions which render them in a physiologically compromised state ideal for mortality from COVID-19.

It is recommended for:

• All geriatric age group patients with symptoms to be admitted to a health care facility, with access to immediate assessment and escalation of treatment when deemed necessary.

• Prior assessment of patient’s comorbid conditions, functional status, and frailty should be documented on initial admission clerking. Efforts should be made to optimize any underlying medication condition right from the admission.

• Efforts to be made to reduce polypharmacy. As an increased number of medications would increase the risk of drug interactions and further complications. Over the phone consultation can be done, where appropriate, to optimize underlying medical conditions and revise medications as necessary.

• Invasive interventions such as Dialysis and Resuscitation status should be discussed with patients and or with relatives and ceilings of treatment escalation should be documented even before patients become critical.

Published case reports from the Chinese Centers for Disease Control indicate patients with underlying comorbid conditions have a heightened risk for contracting COVID-19 and a worse prognosis. Depending on the report, between 25% and 50% of COVID-19 patients present with underlying comorbid conditions (34). At the time of admission, patients’ comorbid status, past surgical and current medical treatments should be documented.

This group of patients are at increased risk of mortality (10.5%) from COVID-19 (32), therefore, they should be treated at a health facility where possible. Attempts should be made to optimize underlying conditions as patients’ progress through stages of infection. Obtain cardiac consultation via phone as necessary.

Regarding ACEI/ARB: At present, there is no enough evidence to indicate harm of continuing ACEI/ARB during COVID-19 treatment, therefore it should not be stopped unless there are other indications such as low BP, development of AKI or hyperkalemia. The morbidity and mortality risk of stopping such drugs are significant, particularly given the myocardial damage


7.2.2 COPD AND CHRONIC LUNG DISEASE

7.2.3 OBESITY AND OHS

that may occur in COVID-19 (35, 36). QT Prolongation: Some of the medications used in COIVD-19 management are known to cause QT prolongation. Therefore, special attention is required to prevent complications related to QT Prolongation. Relative contraindications for medications with Qt prolonging effect includes a history of long QT syndrome, or baseline QTc >500 msec (or >550 msec in patients with QRS greater than >120 msec)

It is recommended to discontinue/and avoid non-essential QT-prolonging agents and document a baseline ECG, serum potassium and serum magnesium.

Refer to Annexe 1 for a list of commonly used QT-prolonging medications and monitoring protocol.

Although the reported prevalence COVID-19 in patients with asthma or COPD is lower than others, COPD is associated with a significant, over five-fold increased risk of severe COVID-19 infection (37).

Those patients with chronic respiratory conditions including COPD and Asthma should continue their regular therapy including inhaled corticosteroids as the potential benefits or harms of these treatments for people at risk of SARS-CoV-2 infection or patients with COVID-19 are unclear at present (38).

Patients with COPD should be changed to MDI with spacer instead of nebulizers while hospitalized unless they have an altered mental status, dementia, etc, which prevent effective use of MDI.

In a patient who is using a home BiPAP, it is advised to continue its use in a facility where there is a single isolated dedicated room or a negative pressure room for the person (to take airborne precautions while attending to such a patient).In a COVID19 patient with underlying chronic lung disease such as COPD, the target spO2 is 88-92%.

Obesity has been shown to increase vulnerability to infections and it may be associated with other risk factors such as metabolic syndrome and obesity-related lung disease. Therefore obesity increases the risk of COVID-19-related mortality (39).

Obese patients have a higher incidence of obstructive sleep apnea and obesity hypoventilation and are at higher risk of respiratory failure (40).

These patients are expected to have difficult airways; therefore, it is important to plan intubation ahead. And ideally, this should be done by the most experienced operator available at the time.

These patients are more difficult to position and transport by nursing staff and obese patients who develop ARDS may not do well when prone.


7.2.4 PATIENTS WITH CANCER AND IMMUNOSUPPRESSIVE STATE

7.2.5 CHRONIC KIDNEY DISEASE IN COVID -19

7.2.6 CONSIDERATION FOR LIVER DISEASE PATIENTS IN THEMANAGEMENT OF COVID-19.

Based on early descriptive studies from China, patients with cancer - particularly those on active treatment for cancer had higher prevalence, higher risk of severe disease, and an elevated risk of death from COVID-19 compared to those without (41). Following considerations are recommended while managing Cancer and Immunosuppressed patients.

• More intensive surveillance for diagnosing Covid-19 infection in these patients. • More aggressive treatment protocols should be considered when patients with cancer are

infected with SARS-CoV-2, especially in older patients or those with other comorbidities (42).

• Locoregional therapies should be postponed whenever possible and immune-checkpoint inhibitor therapy temporarily withdrawn (43)

Patients with existing conditions can be more susceptible to COVID-19 and are likely to experience more severe illness, including patients with chronic kidney disease, patients on chronic dialysis, and those living with a kidney transplant.

Kidney abnormalities associated with increased in-hospital mortality in patients with COVID-19 include proteinuria, hematuria, elevated serum creatinine, elevated blood urea nitrogen, and glomerular filtration rate < 60 mL/minute/1.73 m2 (44).

Patients undergoing regular hemodialysis twice or three times weekly, need to continue their regular dialysis as planned.

Dialysis patients with COVID-19 preferably admitted in the same ward or ICU, when possible, can enable one dialysis care trained nurse to simultaneously deliver care to more than one patient.

Adjust Ultra-filtrate to avoid fluid overload.

Although patients with cirrhosis were found to be at increased risk of decompensation or development of acute-on-chronic liver failure (ACLF) in influenza infection (45), this association is yet not proven in COVID-19 patients due to insufficient data (43).

Recommendations for managing CLD patients with COVID-19 (43).• Invasive measures such as Endoscopy should be limited to life-threatening emergencies

such as UIGB in view of a high risk of dissemination of infection. • Surveillance USG should be deferred until complete recovery. • Patients who are on treatment for decompensated CLD should continue medications to

prevent worsening of decompensation• Prevent acetaminophen overdosing (2-3g/day is safe for Cirrhosis) and avoid NSAIDs

(46).• Cirrhotic patients who are on immunosuppressive therapies such as Cyclosporin,

Tacrolimus, Sirolimus needs to be closely monitored for drug toxicities when other drugs are co-administered.


7.5 CARING FOR PREGNANT WOMEN WITH COVID-19(3)

7.6 CARING FOR INFANTS AND MOTHERS WITH COVID-19: IPC AND BREASTFEEDING

Data is limited on clinical presentation and perinatal outcomes after COVID-19 infection during pregnancy or the puerperium. There is no evidence that pregnant women present with different signs and/or symptoms or are at higher risk of severe illness. So far, there is no evidence on mother-to-child transmission when infection manifests in the third trimester, based on negative samples from amniotic fluid, cord blood, vaginal discharge. Similarly, evidence of increased severe maternal or neonatal outcomes is uncertain, and limited to infection in the third trimester, with some cases of premature rupture of membranes, fetal distress and preterm birth reported (3).

Pregnant women with a suspected, probable or confirmed COVID-19 infection, including women who may need to spend time in isolation, should have access to woman-centred care including obstetric, neonatal care, as well as mental health and psychosocial support, with readiness to care for maternal and neonatal complications. These patients should be managed by a multidisciplinary team including obstetrician, paediatrician, physician and when needed anesthesiologists (3).

Clinical management of a pregnant patient will be the same as a non-pregnant patient. Prior to taking X-ray/CT when required, informed consent should be taken from the patient and necessary abdominal protection measures should be taken.

COVID-19 infection is not an indication for termination of pregnancy and the timing should be individualized. The indications for termination of pregnancy depend on the mother’s condition, gestational age, and fetal wellbeing. When there is an indication, active termination of pregnancy may be considered at the same time as treatment. If fetal lung maturation is required before termination of pregnancy, all patients should receive two doses of Betamethasone 12mg IM – 2 doses 24hours apart (47).

It is inconclusive whether vaginal delivery or cesarean delivery is safer. The consensus of the obstetric team is to prefer LSCS unless delivery is imminent (47).

Neonatal throat swab and breastmilk samples from mothers after the first lactation was found to be negative for SARS-CoV-2. Nevertheless, after birth, a newborn is susceptible to person-to-person spread (3).

The consensus of the pediatric team is to avoid breastfeeding, however, each case may be individualized based on the wish of the couple /severity of disease and local disease context (47).

The newborn of those mothers suspected or diagnosed with COVID 19 infection should be isolated for 14 days. Prior to discharge, it is recommended to test for COVID 19, and de-isolate if the test is negative.


Mental Health aspects of COVID-19 and care of patients with Psychiatric Conditions

8

COVID-19 patients are at high risk of mental health sequelae due to fundamental concerns such as social isolation, stigmatization, loss of control and uncertainty towards the outcome. Studies from Chinese COVID-19 patients reported as high as 96% PTSD rate (48), Of those who died, 22% had delirium compared to 1% of those who survived (49). Increased age, history of dementia coupled with ICU treatment would make patients prone to psychiatric elements such as delirium, anxiety/panic attacks, psychomotor agitation, depression and suicidality which adversely affects outcome.

A patient-centred holistic approach is needed to reduce anxiety, delirium and depression during the active phase of treatment. Online psychiatric consultation can be sought for these patients to assess their symptoms, assess mental capacity and to guide treatment. Finally, supporting family members of COVID-19 patients also have to be considered to assist families to cope with the situation.

Recommendations: (50,51)

• Consider administering PHQ 9 and GAD-7 scoring on admission for patients who are at risk of anxiety and depression to risk stratify and repeat as needed (Refer to Annexe 6).

• Obtain over the phone Psychiatric referral for high risk patients.

• Special attention in geriatrics to prevent/reduce delirium (Refer to table 25).

• Avoid antipsychotics unless self-harm, severe agitation.

• Use CAM ICU score to assess patients with delirium (Refer to Annexe 6).

• Involve Social Services where necessary to facilitate communication with families of the affected.

Quetiapine

LorazepamSertraline

HaloperidolIf refractory use OlanzapineOr Quetiapine

Re-orientationDaylight when possible, bedside mobility as much possibleMinimize tethers- iv lines/catheters/ECG leads/physical restraints when possiblePrevent constipation and dehydrationWhenever possible allow interaction with family via Phone/video/picturesMinimize sensory deprivation- such as spectacles and hearing aids).

W/out Delirium 12.5-25mg SOS With Delirium 12.5-25mg TDS

0.5-2mg SOS/TDS25mg-50mg OD

0.5-1mg iv Q6H, 1-2mg PO Q6H2.5-5mg Q12H. 12.5-25mg HS

Psychiatric Symptoms Drug Option Dosage Option

Anxiety/PTSD

Pharmacologicalmanagementofdelirium

Non-PharmacologicalManagementofdelirium

Table 25Management of Anxiety/PTSD and Delirium


Palliative Care and symptom control in terminally ill COVID-19 patients(52)

9Our duty to treat patients with respect and dignity is always at the forefront of the care we provide. Accordingly, we should understand patients’ goals of care and offer only those interventions that are consistent with such goals. This is particularly important during this public health crisis, regardless of whether the patient is COVID-19 positive or is presenting with other serious illness. Time permitting, all care teams should discuss patient goals and wishes as soon as possible in the course of any illness and with a change in the patient’s clinical status.

Most common symptoms of COVID-19 in terminal patients are pyrexia, dyspnoea, and secretions. It is important to address these symptoms to provide comfort-focused care during the terminal stage of illness. On the other hand, palliative sedation as a resort to end-of-life-care management may have its drawbacks including paradoxical agitation and distress among family members or health care staff due to the inability to interact with patients.

Pre-emptive discussion between the patient/patient-party and the treating team, which includes physicians and psychiatrist, is needed before starting sedative medications to reduce the problem of palliative sedation.


Use Opioids • Mild symptoms- oral• Moderate- severe- IV/SC• 2-4mg Morphine IV/SC SOS. Use

infusion 1-2mg/hr, if it requires frequent boluses.

• Use Fentanyl if Renal impairment. • 25-50mcg SOS • Can switch to continuous infusion

if it requires frequent boluses. Start at 10mcg/hr and titrate up for comfort.

• May use additional SOS boluses on top of infusion for breakthrough symptoms.

Use Benzodiazepine for anxiety without disorientation. • Alprazolam 0.5mg PO SOS/ TDS• Lorazepam 1-2mg PO Q8/6H.Use Antipsychotics for anxiety with disorientation• Olanzapine 2.5-5mg P Q6H/SOS• Haloperidol 1-2mg IV Q2H/SOS• Explore spirituality and facilitate as

possible.

• Haloperidol 2-4mg IV Q2H, Olanzapine 2.5-5mg PO Q6H/SOS

• Quetiapine 25-50mg PO Q8H• Avoid Haloperidol or Olanzapine in

Parkinson, Lewy Body Dementia

• Paracetamol 0.5-1g H4/q8H• Panadeine 1 tab TDS• Morphine 2-4mg Q2-4H/SOS• Fentanyl 25-50mcg Q2H/SOS

• Lactulose 15ml HS• Cremaffin 15ml HS

• Bedside assessment of dyspnea severity

• Treat reversible causes • Escalate opioids for optimum

comfort while avoiding side effects.

• Often anxiety coexists with dyspnoea.

• ICU setup with inability to see the family is likely going to make anxiety symptoms worse.

• Use non-conventional measures such as video calls to see family

• Employ delirium prevention measures.

• Delirium and agitation might be the first sign of clinical deterioration.

• Rule out reversible causes before up titrating narcotics or antipsychotics

• Opioid is the quickest way to relieve pain.

• Try to avoid NSAIDs

Nausea/vomiting Constipation Drowsiness Respiratory Depression Constipation

QT prolongation Respiratory depression

QT prolongation. Extrapyramidal Symptoms Drugs may worsen delirium

Reduce the dose of paracetamol if the liver is deranged.

Narcotics cause constipation, respiratory and CNS depression.

Watch for loose stool Avoid if SAIO

Symptoms Medications Things to watch for

Dyspnoea

Anxiety

TerminalDelirium/Agitation

Pain

Constipation

Table 26Summary of comfort-focused care management for palliation. (Note: Doses used for management of symptoms with palliative intent might be higher than usual doses, the aim is to keep dying patients’ symptoms free as much, while avoiding medication side erects and over sedation)


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Figure 13Guidance on starting Hydroxychloroquine and QTc monitoring (Adapted from ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic)

Figure 14Measurement of QTc and normal values

Measurement of QTc

Bazett’s corrected QTc formula = QT/√RR

Normal QTc:♂< 450ms♀< 470ms


Figure 15Depicts an ECG of Torsades de Pointes (TdP)

Table 27Commonly used drugs that prolong QT interval

Drugs that prolong QT Interval

• Azithromycin• Ciprofloxacin• Chloroquine • Erythromycin• Fluconazole• Itraconazole• Levofloxacin• Moxifloxacin

• Amiodarone • Amitriptyline• Escitalopram• Fluoxetine • Sertraline

• Chlorpromazine• Haloperidol • Quetiapine • Risperidone • Domperidone

• Ondansetron

• Phenytoin • Ritonavir

• Indapamide • Oxytocin• Ranolazine• Hydroxychloroquine

Antimicrobials Antiarrhythmics Antidepressants Antipsychotics

Antiemetics

Anticonvulsants Antivirals

Others:


Annexe 2Awake Proning Guide

Aims

Duration

Bed Positioning

Head Positioning

Placement for patient poistioning

Awake proning may reduce ICU admissions. Intubation in COVID-19 has a high mortality.Patient must be a awake and willing to comply.

Aim to remain prone for 4 hours periods. Allow 1 hour comfort breaks between periods of proning for eating, drinking, toilet and general comfort.

Steep head up (at least 30 degrees).

Leave oxygen mask in place - do not try and wean down yet. Improvement of oxygenation with proning may take many hours to manifest.

Head turned to left or right - whatever is comfortable for the patient.

Alternatively head in neutral position using a travel pillow (face in hole.)

NB: The abdomen should hang free and not be compressed. This is even more important in obese patients.

• 1 soft pillow for the head• 2 substantial pillows for under the chest• 2 substantial pillows for under the pelvis• 1 pillow for under the shins

Figure 16 Awake proning guide (Adapted from Awake proning guide NHS)


Awake Proning ProtocolThis is the protocol for proning for Spontaneous Breathing Patients

Indication: If Covid – 19 Patient diagnosed or Suspected requiring FiO2 > 0.6 to maintain SpO2 > 92%, if with other comorbidities (COPD/ILD) SpO2 >88%: without any contraindications for Prone position.

Discontinue proning if there is no improvement after change of positions, patient experiencing discomfort or if RR>35/min with use of accessory muscles.

Allow Prone position in reverse trendelenberg position.

Ineachpositionfor30minutesto2hours

Prone position -> Right Decubitus position -> Sitting position -> Left Decubitus position -> Proneposition

Monitor Saturation after every position change

Monitorforabout15minutes.

Do not sedate the patient to facilitate proning

Respiratory distress ((RR>35, PaCO2 > 6.5, accessory muscle use

Immediate need for intubation

Hemodynamic instability SBP <90mmHg, or arrhythmia

Agitation/ altered mental status

Unstable spine fractures/ recent abdominal surgery

Facial Injury

Neurological issues (seizures)

Morbid obesity

Pregnancy 2nd/3rd Trimester

Pressure sores/ ulcers

Absolute contraindications Relative Contraindications

Table 28Contraindications for Proning


Annexe 3Predicted Body Weight and Tidal Volume Tables

PBW & Tidal Volumefor Females

PBW & Tidal Volumefor Males

Table 29Tables of predicted body weight and Tidal volumes for Males and Females.Adapted from ARDSNet


Annexe 4Em

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Figure 19Algorithm for intubationSource: https://onlinelibrary.wiley.com/doi/full/10.1111/anae.15054


Figure 20Algorithm for intubationSource: https://onlinelibrary.wiley.com/doi/full/10.1111/anae.15054


Annexe 5Richmond Agitation - Sedation Scale

Combative

Very Agitated

Agitated

Restless

Alert & Calm

Drowsy

Light Sedation

Moderate Sedation

Deep Sedation

Unarousable

+4

+3

+2

+1

0

-1

-2

-3

-4

-5

Combative, violent, immediate danger of staff

Pulls or removes tube(s) or catheter(s); aggresive

Frequent non-purposeful movement, fights ventilator

Anxious, apprehensive but movement are not aggresive or vigorous

Not fully alert but has sustained awakening to voice (eye opening & contact greater than 10 seconds)

Briefly awakens to voice(eye opening & contact less than 10 seconds)

Movements or eye opening to voice(but NO eye contact)

No response to voice, but has movement or eye opening to physical stimulation

No Response to voice or physical stimulation

Target RASS Value RASS Description

Table 30Richmond agitation - sedation scale


Annexe 6PHQ 9 Questionnaire and applications

PHQ-9 score ≥10 (for major depression)- Sensitivity: 88%, Specificity: 88% (62)


Annexe 7GAD -7 Questionnaire

Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety. Scores more than 10: suggest significant anxiety. CAM-ICU


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