Category : Sepsis Guidelines

Developing local guidelines for management of sepsis in adults: Sepsis Guidelines for Pakistan (SGP)

Endorsed by Global Sepsis Alliance

Madiha Hashmi1*, Fazal Hameed Khan1, Ali bin Sarwar Zubairi1, S. Tipu Sultan2, Saeeda Haider3 Sadqa Aftab4, Javed Husain5, Anwar ul Haq1, Zahid Akhtar Rao6, Amin Khuwaja7, Syed Farjad Sultan3, Zunairah Rais8, Roohina Baloch9, Naseem Salahuddin3, Aslam Khan10, Faisal Sultan11, Kamran Chima12, Amjad Ali13, Gohar Ali14; Pakistan Society of Critical Care Medicine; Pakistan Society of Anaesthesiologists; Medical Microbiology & Infectious Diseases Society of Pakistan and Pakistan Chest Society.

1Aga Khan University, Karachi

2Sind Institute of Urology and Transplant, Karachi

3The Indus Hospital, Karachi

4Dow University of Health Sciences and Civil Hospital, Karachi

5South City Hospital, Karachi

6PNS Shifa Hospital, Karachi

7National Institute of Cardiovascular Diseases, Karachi

8Liaquat National Hospital, Karachi

9Jinnah Post Graduate Medical Center, Karachi

10Military Hospital, Rawalpindi

11Shaukat Khanum Memorial Hospital and Research Center, Lahore

12 Services Institute of Medical Sciences, Lahore

13Bolan Medical College, Quetta

14Lady Readings Hospital, Peshawar

*Correspondence: Madiha Hashmi, President PSCCM, Director SICU and Assistant Professor

Department of Anaesthesiology, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi 74800 (Pakistan); E-mail: hashmi_madiha@yahoo.ie

ABSTRACT

Background: The purpose of developing ‘Sepsis Guidelines for Pakistan’ (SGP) is to provide clinicians practicing in local hospitals with a framework to aid timely recognition and management of adult patients in sepsis by adopting evidence-based recommendations of  Surviving Sepsis Campaign (SSC)  tailored to available resources. These recommendations are not meant to replace the SSC Guidelines.

Methodology: SGP is an initiative of Pakistan Society of Critical Care Medicine (PSCCM). Four key decision points to be addressed in the guidelines were identified by a thirteen member multidisciplinary committee i.e., grading the hospitals in the country, recognition of sepsis and associated organ dysfunction, essential interventions to manage sepsis, and general measures for provision of a comprehensive care to patients in sepsis according to the level of education and training of healthcare providers and facilities and resources available in different levels of hospitals. The draft was presented at the 3rd Sepsis Symposium held on 13th September, 2014 in Karachi. The final document was approved by a panel of experts from across the country, representatives of relevant societies and Global Sepsis Alliance (GSA).

Recommendations: Hospitals are divided into basic, intermediate and tertiary depending on the availability of diagnostic facilities and training of the medical personnel. Modified definitions of sepsis, severe sepsis, and septic shock are used given the lack of facilities to diagnose sepsis according to international definitionsand criteria in Pakistan. Essential interventions include fluid resuscitation, vasopressors to support the circulation, maintaining oxygen saturation ≥ 90% with oxygen, non-invasive ventilation or mechanical ventilation with lung protective strategies, prompt administration of antibiotics as recommended by the Medical Microbiology & Infectious Diseases Society of Pakistan (MMIDSP) and early source control. It is recommended to avoid starvation, keep an upper blood glucose ≤180 mg/dL, use daily pharmacoprophylaxis against venous thromboembolism (VTE), use stress ulcer prophylaxis, target haemoglobin of 7-9 g/dl in the absence of  ischaemic heart disease, avoid sodium bicarbonate therapy as long as pH > 7.20, avoid fresh frozen plasma in the absence of bleeding, transfuse platelets if indicated, not use intravenous immunoglobulins and avoid neuromuscular blocking agents (NMBAs) in the absence of ARDS, target specific titration endpoints when continuous or intermittent sedation is required in mechanically ventilated patients and use continuous renal replacement therapy (CRRT) to facilitate management of fluid balance in hemodynamically unstable septic patients in tertiary care centers. In addition a comprehensive, meticulous and multidisciplinary general care is required to improve outcome of sepsis by reinforcing hand hygiene and other infection control measures, adequate monitoring and documentation tailored to the available resources.  Goals of care and prognosis should be discussed with patients and families early and either shifting the patient to a hospital with better facilities or limiting or withdrawing therapy in case of poor prognosis should be considered.

Key words:Sepsis syndrome; Septic shock; Hypotension; Sepsis

Citation: Hashmi M, KhanFH, Zubairi ABS, Sultan ST, Haider S, Aftab S, Husain J, Haq AU, Rao ZA, Khuwaja A, Sultan SF, Rais Z, Baloch R, Salahuddin N, Khan A, Sultan F, Chima K, Ali A, Ali G; Pakistan Society of Critical Care Medicine; Pakistan Society of Anaesthesiologists; Medical Microbiology & Infectious Diseases Society of Pakistan; Pakistan Chest Society. Pakistan Society of Critical Care Medicine: Developing local guidelines for management of sepsis in adults: Sepsis Guidelines for Pakistan (SGP). Anaesth Pain & Intensive Care 2015;19(2):196-208

  1. INTRODUCTION

The Surviving Sepsis Campaign (SSC)1 Guidelines provide a framework for clinical decisions in the management of severe sepsis and septic shock.Despite their obvious benefits2,3, the SSC guidelines have not been fully implemented in low and middle income countries (LMIC) due to lack of awareness, limited resources, financial constraints and a wide variation in the available healthcare facilities within most of the countries falling in the LMIC category4,5,6,7. Even in Pakistan the healthcare facilities range from well-equipped urban university hospitals to small hospitals lacking qualified medical personnel or basic life-saving equipment.

Most of the interventions in the resuscitation and treatment bundles recommended by SSC are independent therapies based on evidence and inability to comply with the full ‘bundle’ should not prevent the healthcare workers from implementing part of the ‘bundle’. The purpose of developing ‘Sepsis Guidelines for Pakistan’ is to provide clinicians practicing in local hospitals with a framework to aid timely recognition and management of adult patients in sepsis by adopting evidence-based recommendations of  SSC tailored to available resources. These recommendations are not meant to replace the SSC Guidelines.

The ultimate goal of developing Sepsis Guidelines for Pakistan is to reduce the unacceptable and undesirable variation in practice of healthcare professionals from different disciplines and different healthcare set ups and to improve sepsis outcomes.

  1. METHODOLOGY

Sepsis Guidelines for Pakistan (SGP) is an initiative of Pakistan Society of Critical Care Medicine (PSCCM). The executive committee of PSCCM (Karachi Chapter) convened in 2014 and formed a multidisciplinary committee of physicians managing critically ill patients in teaching and non-teaching hospitals of Karachi in both government and private healthcare setup. The thirteen member committee consisted of eight anaesthesiologists, three pulmonary and critical care physicians, one full time intensivist, and one paediatric intensivist- all heading the intensive care units in their respective hospitals. No external funding was used and none of the authors had any financial conflict of interest in drugs or techniques discussed in the manuscript.

The task of the committee was to recommend interventions to recognize sepsis and associated organ dysfunction and to institute essential therapies according to available resources targeting all healthcare workers entrusted with the care of adult patients in sepsis.

Step 1: Key decision points:

Based on informal consensus discussions amongst the members of the committee, following key decision points to be addressed in the guidelines were identified;

  • Grading the hospitals in the country
  • Recognition of sepsis and associated organ dysfunction according to the level of education and training of healthcare providers and diagnostic facilities available in different levels of healthcare setup.
  • Essential interventions to manage sepsis according to facilities and resources available in different levels of healthcare setup.
  • General measures for provision of comprehensive care to patients in sepsis according to facilities and resources available in different levels of healthcare setup.

Step 2: Literature and evidence:

Expert opinion and clinical experience of the authors working in hospitals with a wide variation in available resources was considered to grade the healthcare facilities in three categories. Interventions to address rest of the key decision points were based on 2012 Surviving Sepsis Campaignguidelines for the management of severe sepsis and septic shock1 and relevant literature for implementing these guidelines in resource poor settings was reviewed. Five articles on sepsis management from resource-limited settings were selected by consensus8,9,10,11,12 from a reference list prepared by conducting a structured literature review using the key words sepsis, management, resource-limited, resource poor and low-middle income countries. The coordinator of the committee circulated the key background material electronically to all members of the committee. A list of all possible interventions recommended in these articles was prepared. Feasibility of each intervention was debated in view of availability of resources and training of medical personnel in different healthcare facilities and accepted, rejected or modified based on the majority vote of the members of the committee. If an intervention was accepted as recommended by SSC, the original assessment of quality of evidence and strength of recommendations was quoted. None of the committee members were trained in application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) system so in case an intervention was modified we did not use the GRADE system but mentioned that the recommendation was based on ‘consensus opinion’.

           Quality of evidence

A

High

B

Moderate

C

Low

D

Very Low

UG

Ungraded

    Strength of Recommendations

Grade 1

Strong

Grade 2

Weak

Step 3: Drafting the Document:

The chairman of the SGP Committee prepared a draft of the proposed guidelines and circulated amongst the members of the committee. In-person discussions were held at the PSCCM monthly meetings to improve the draft. Disagreements amongst the members were resolved by adopting a consensus process. The draft was approved by all committee members and was presented in 3rd Sepsis Symposium held on 13th September, 2014 at Avari Hotel, in Karachi to commemorate the 3rd World Sepsis Day. Comments from audience and input from the founding member of MMIDSP were incorporated by the Chairman of the committee. The document was then reviewed by outside-committee experts from rest of the provinces of Pakistan, i.e. Punjab, Baluchistan, and Khyber Pakhtunkhwa. Guidelines were also presented in a tabulated format for easy retrieval and assimilation of information applicable to the various grades of the existing healthcare facilities.

Step 4: Dissemination Plan:

Multifaceted interventions will be utilized to disseminate and implement the guidelines. Anaesthesiologists are the backbone of critical care in Pakistan, supported by pulmonary and critical care physicians. The guidelines will be propagated from the platform of Pakistan Society of Critical Care Medicine (PSCCM), Pakistan Society of Anaesthesiologists (PSA), Infectious Diseases Society of Pakistan (IDSP) and Pakistan Chest Society (PCS) in the form of presentations in the respective annual conferences. Posters based on a flow-chart format will be created for dissemination.

  1. RECOMMENDATIONS
  2. Grading the Hospitals according to available resources:
  3. BASIC: Hospitals that have no intensive care unit backup and where only general physicians are available as medical personnel. These have access to outsourced laboratory facilities but there are no on-site radiological diagnostic facilities.
  4. INTERMEDIATE: Hospitals with level-2 intensive care units that are managed by non-intensivist medical personnel. These have access to in-house basic laboratory and diagnostic radiological facilities.
  5. TERTIARY:  Hospitals with level-3 intensive care units, that are managed by physicians trained in intensive care medicine. These have access to advanced laboratory and diagnostic radiological facilities.

This grading is arbitrary and there will be hospitals that fall in-between the above mentioned categories. The aim of providing this framework is to allow the users to acknowledge the resources available in their hospitals. The available resources should be utilized to recognize sepsis, severity of organ dysfunction and the most likely source of infection and to provide essential interventions to manage sepsis or consider transfer to another hospital with better facilities.

  1. Recognition of sepsis and associated organ dysfunction (Table 1):

Recognizing a patient in sepsis is an essential step for effective treatment. A delay in diagnosis results in progression of sepsis and decreases chances of survival. Modified definitions of sepsis severe sepsis, and septic shock have to be applied given the lack of facilities to diagnose sepsis according to international definitions13 and criteria in Pakistan.

a. SEPSIS:

Sepsis is defined as proven or highly suspected infection associated with some of the following conditions:

  • Altered mental state/confusion
  • Temperature ≥38°C or ≤ 36°C
  • Heart rate ≥90 bpm
  • Respiratory rate ≥ 20 bpm or PaCO2 ≤ 32 mmHg
  • WBC ≤ 4000 /mm3or ≥ 12000/mm3 or ≥ 10% immature forms
  • Thrombocytopenia (platelet count, ≤ 100,000/mm3)
  • Hyperglycemia (plasma glucose > 140 mg/dL in the absence of diabetes)

b. SEVERE SEPSIS:

When ‘sepsis’ leads to tissue hypoperfusion or organ dysfunction it becomes ‘severe sepsis’.

        i.      TISSUE HYPOPERFUSION

  • Systolic blood pressure ≤ 90 mmHg or a systolic blood pressure decrease ≥40 mmHg from the baseline or mean arterial pressure (MAP) ≤ 65 mmHg.
  • Decreased capillary refill or skin mottling

ii.      ORGAN DYSFUNCTION:

a)      Pulmonary dysfunction:

  • Signs of respiratory distress (i.e., dyspnea, added sounds on auscultation, cough, sputum)
  • Arterial Hypoxaemia (PaO2/FiO2  ≤ 300)

b)     Renal dysfunction

  • Acute oliguria (urine output ≤ 0.5 ml/kg/h for at least 2 h despite adequate fluid resuscitation)
  • Creatinine increase ≥ 0.5 mg/dL

c)      Hepatic dysfunction

  • Jaundice
  • Hyperbilirubinaemia (plasma total bilirubin ≥ 4 mg/dl)

d)     Coagulation dysfunction

  • Petechae or ecchymosis
  • Bleeding/oozing from puncture sites
  • Coagulation abnormalities (INR ≥1.5 or aPTT ≥ 60 s)

e)      Gastrointestinal dysfunction 

  • Ileus (absent bowel sounds)

c. SEPTIC SHOCK

When sepsis-induced hypotension or signs of tissue hypoperfusion persist despite adequate fluid resuscitation, the condition is labeled as ‘septic shock’.

3. Essential interventions (Table 2):

Essential interventions refer to treatments recommended to be administered without delay to maintain a near normal physiology.  The compromised organ systems need support while identification of source of sepsis and its control is of paramount importance. Although these essential interventions are presented in a certain order, they may have to be performed simultaneously, depending on the condition of the patient.

a. Circulation

  • Fluid resuscitation in patients with sepsis induced tissue hypoperfusion or organ dysfunction is the corner stone of sepsis management. Initial fluid challenge of a minimum of 20-30 ml/kg should be followed by continuous infusion for 24–48 h, though a more rapid administration and larger volume of fluid may be needed in some patients (grade 1C). Use of crystalloids is strongly recommended (LoE: 1B) because synthetic colloids have shown to precipitate acute kidney injury and should be avoided (LoE: 1B).   Albumen can be used if excessive fluid requirement has a risk of aggravating tissue or pulmonary oedema or precipitating abdominal compartment syndrome (LoE: 2C).
  • In the basic setup, the clinicians should target an improvement in pulse volume, capillary re-fill, level of consciousness, urine output and a systolic arterial blood pressure > 90 mmHg, while frequently auscultating the chest for any sign of fluid overload (consensus opinion). If resources are available target for a mean arterial pressure (MAP) > 65 mmHg, CVP 8-12 mmHg, and urine output > 0.5 ml/kg/hr (LoE: 1C). In tertiary care hospitals target for ScvO2 more than 70% and to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion (LoE: 2C).
  • Use of vasopressors is recommended in patients with persistent hypotension (MAP < 65) despite initiating fluid resuscitation (LoE: 1C). Norepinephrine is the vasopressor of choice (LoE: 1B) but dopamine can be used in selected patients in whom risk of tachyarrhythmias is low or they have absolute or relative bradycardia (LoE: 2C) or if norepinephrine is not available (consensus opinion).  Epinephrine worsens metabolic acidosis and should be used in septic patients only when an additional agent is needed to maintain adequate blood pressure (grade 2B). Vasopressin at a rate of 0.03 units/minute can be added to norepinephrine (NE) to raise MAP or decrease NE dosage (UG), when available in a tertiary care setup. In patients requiring vasopressors, central access should be taken safely and invasive arterial blood pressure measured continuously (consensus opinion).
  • Intravenous hydrocortisone (50 mg every six hours) should be administered if haemodynamic targets are not met with adequate fluid resuscitation and dose requirement of vasopressors rapidly escalates (LoE: 2C).

b. Ventilation:

  • Oxygen saturation should be kept ≥ 90%. If pulse oximeter is not available patients with severe sepsis or septic shock should be given oxygen empirically (consensus opinion). If hypoxaemia persists despite oxygen therapy, use of non-invasive ventilation (NIV) is recommended, provided medical staff is adequately trained in its use (LoE: 2B) and patient is awake and able to clear and protect the airway. However a low threshold for endotracheal intubation should be maintained.
  • For mechanical ventilation of patients with sepsis induced ARDS, lung protective strategies should be used i.e. a tidal volume of 6-8 ml/kg of predicted body weight (LoE: 1A), adequate PEEP to avoid alveolar collapse (LoE: 1B) and measuring and keeping plateau pressure < 30 mmHg (LoE: 1B). Mechanically ventilated patients should be placed in a semi-recumbent position (head of the bed raised to 30–45°) to reduce the risk of aspiration and ventilator-induced pneumonia, unless contraindicated (LoE: 1B).
  • Lung recruitment maneuvers and prone positioning is recommended to manage severe hypoxaemia (PaO2 /FiO2 <100), in tertiary care setup, according to the hospital protocols (LoE: 2C).

c. Antimicrobial therapy

Prompt administration of appropriate intravenous antimicrobials to cover the most likely infection should be the goal of therapy.

  1. MMIDSP Recommendations before selecting empirical antibiotic therapy:
  • Selection of antibiotic must be based on clinical assessment of site of infection
  • Viraemia, severe malaria or fungaemia must be considered as possible causes of sepsis
  • Antibiotics must be administered as soon as possible, within 2 hours of admission to ER or ICU
  • Two sets of blood cultures, urine analysis and urine culture must be drawn prior to institution of antibiotic
  • Obtain history of previous use of antibiotics in past 3 months. Avoid same antibiotic if possible
  • Dose must be prescribed on weight basis
  • Dose must be adjusted for renal or hepatic insufficiency
  • Hematologic malignancy or febrile neutropenia must be considered
  • Combination therapy may be prescribed for suspected highly resistant pathogens
  • Only intravenous antibiotic should be used until there is clinical improvement

2. MMIDSP Recommendations during antibiotic therapy:

  • Once culture and sensitivity reports are available, de-escalate to a narrower spectrum antibiotic
  • Once patient shows clinical improvement and is stable, de-escalate to oral preparation, if an equally effective oral preparation is available
  • Antibiotic should be given for no longer than 7-10 days
  • Source control is essential, i.e. drainage of abscess, repair or resection of perforated viscus, removal of cannula, catheter or devices and debridement of infected tissue.

d. Source control

  • A detailed history of illness from the patients or the relatives along with a thorough clinical examination is essential to identify the likely source of infection.
  • Appropriate imaging techniques should be utilized for specific anatomical diagnosis of infection and surgical and interventional radiology expertise sought as early as feasible for source control.
  • Implants, devices, or central lines should be removed if suspected to be the source of infection.
  • Use of oral chlorhexidine gluconate should be promoted in mechanically ventilated patients in intermediate and tertiary care set up as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia (LoE: 2B).

e.  Nutrition

Complete fasting should be avoided in septic patients and oral or tube-feeding should be started within the first 48 hours after a diagnosis of sepsis (LoE: 2C). Feed should be started with 500 calories per day and gradually advanced as tolerated (LoE:2B). Total parenteral nutrition (TPN) alone or to supplement enteral feeding is not recommended in the first 7 days of a severe infection (LoE: 2B).

f. Other measures

  • Two consecutive blood glucose levels >200 mg/dL should prompt initiation of intravenous insulin infusion with an aim to keep an upper blood glucose ≤180 mg/dL Blood glucose values should be monitored frequently until glucose values and insulin infusion rate stabilizes.  Intermediate and tertiary care hospitals should exercise a protocolised approach to blood glucose management in patients with severe sepsis (consensus opinion).
  • Daily pharmacoprophylaxis against venous thromboembolism (VTE) is recommended according to the hospital policy (consensus opinion).
  • When stress ulcer prophylaxis is indicated in patients with severe sepsis/septic shock due to the presence of  bleeding risk factors, proton pump inhibitors should be preferred over H2 -receptor blockers (LoE: 2D).
  • Sodium bicarbonate therapy should be used to improve hemodynamics or reduce vasopressor requirements only if there is life threatening lactic acidosis i.e. pH < 7.20 (consensus opinion).
  • In the absence of bleeding and myocardial ischaemia target haemoglobin of 7-9 g/dl or 10 g/dl if there is a history of ischaemic heart disease (consensus opinion). Fresh Frozen Plasma should not be transfused in the absence of bleeding only to correct lab abnormalities. Transfuse platelets if <10,000/mm3 and no risk of bleeding, <20,000/mm3 if there is significant risk of bleeding and < 50,000/mm3 if bleeding continues, or patient going for surgery or invasive procedure.
  • Intravenous immunoglobulins are not indicated in adult patients with severe sepsis or septic shock (LoE: 2B).
  • Neuromuscular blocking agents (NMBAs) should be avoided if possible in the septic patient without ARDS. Target specific titration endpoints when continuous or intermittent sedation is required in mechanically ventilated patients (LoE: 1B)
  • Renal replacement therapy may be required in patients with severe sepsis and acuterenal failure in tertiary care hospitals. Use of continuous therapies (CRRT) facilitates management of fluid balance in hemodynamically unstable septic patients (LoE: 2D).
  1. General considerations:

A comprehensive, meticulous and multidisciplinary general care is required in addition to therapies targeted at optimizing organ function and eradicating the source of infection in order to improve outcome of sepsis. The level of monitoring, documentation and investigations will depend upon the level of training of medical personnel and available resources. Hand hygiene and other infection control measures should be adopted enthusiastically. It is also important to discussgoals of care and prognosis with patients and families early and consider either shifting the patient to a hospital with better facilities or limit or withdraw therapy in case of poor prognosis.

D. CONCLUSION

A multidisciplinary national panel of experts developed consensus sepsis guidelines to streamline provision of uniform sepsis care and improve sepsis outcome. The guidelines provide a framework to identify sepsis and associated organ dysfunction in a timely manner and recommend essential interventions, taking into account the knowledge and training of medical personnel and resources available in various grades of hospitals in Pakistan.

E. ACKNOWLEDGEMENT

  1. Prof. Konrad Reinhart
    Chairman Global Sepsis Alliance
    Director Dep. for Anaesthesiology and Intensive Care
    Jena University Hospital
    Germany
  1. Niranjan Kissoon
    Vice President Medical Affairs
    BC Children’s Hospital and Sunny Hill Health Centre for Children
    UBC & BC Children’s Hospital Professor in Critical Care – Global Child Health
    Department of Pediatrics and Emergency Medicine, UBC
    Vancouver, Canada
  1. Professor Flavia Machado
    Chair of Anesthesiology, Pain and Intensive Care Department
    Federal University of Sao Paulo
  1. Ron Daniels
    Chief Executive- Global Sepsis Alliance
    CEO- UK Sepsis Trust
    Clinical Adviser (Sepsis) to NHS England
    UK
  1. Professor Simon Finfer
    Senior Staff Specialist in Intensive Care
    Royal North Shore Hospital of Sydney and Sydney Adventist Hospital
    Australia

TABLE 1: SEPSIS RECOGNITION

 

Basic setup

Intermediate setup

Tertiary care setup

 

  • Recognize sepsis

 

 

 

  • Recognize organ dysfunction

 

  • Temperature ≥ 38°C or ≤ 36°C
  • Heart rate ≥ 90 bpm
  • Respiratory rate > 20 bpm
  •  Altered mental state/confusion

 

  • Systolic blood pressure < 90 mmHg
  • Decreased capillary refill or mottling
  • Laboured/difficult breathing
  • Decreased urine output reported by patient or family
  • Ileus (absent bowel sounds)
In addition

  • WBC ≤4000 or ≥ 12000 /mm3  or ≥ 10% immature forms
  • Hyperglycemia (plasma glucose > 140 mg/dL in the absence of diabetes)

In addition

  • Urine output <0.5ml/kg/hr for > 2 hrs
  • Platelet <100,000/mm3
  • Creatinine > 2 mg/dl
  • INR >1.5
  • Bilirubin > 2 mg/dl
  • Acute Lung Injury with PaO2/FiO2 <300
  • Plasma C-reactive protein>2SD above normal
In addition

  • Significant edema or positive fluid balance (> 20 mL/kg over 24 hr)

 

 

In addition;

  • Serum Lactate > 1 mmol/L (or above the reported normal range of the laboratory)

WBC = white blood cells, INR = international normalized ratio, PaO2 = partial pressure of arterial oxygen

FiO2 = fractional inspired oxygen

TABLE 2:ESSENTIAL INTERVENTIONS

 

Basic setup

Intermediate setup

Tertiary care setup

Circulation

  • Oral rehydration salts
  • Iv fluid bolus of a crystalloid (20-30ml/kg), guided by clinical assessment of pulse, BP, capillary re-fill, chest auscultation and level of consciousness
  • Consider shifting to a hospital with ICU facility if no response to fluid replacement or deterioration in general condition

 

 

 

 

WARNING:

  • Avoid synthetic colloids during resuscitation
  • Fluid management using crystalloids and targeting;
  • MAP > 65mmHg
  • Urine output > 0.5ml/kg/hr
  • CVP 8-12 mmHg
  • Use vasopressor (norepinephrine is first choice vasopressor but use dopamine if NE is not available) infusion through a central line if targets not met after 2000ml fluid replacement.
  • Consider iv low dose corticosteroids (50mg 6 hourly) if vasopressor support is rapidly escalating

WARNING:

  • Give vasopressors through a central line
  • Use single lumen femoral vein access if inexperienced or coagulopathy identified

In addition

  • Target mixed venous oxygen saturation >70%
  • Normalize lactate levels
  • Use albumin if fluid requirement > 30ml/kg.
  • Add vasopressin (0.03 units/minute) to raise the BP or reduce the dose of norepinephrine

 

 

 

 

 

 

WARNING:

  • Preferably use triple lumen internal jugular central venous access

Ventilation

  • Supplement oxygen via face mask at 6-10 L/min
  • NIV (CPAP or BIPAP) guided by ABG analysis
  • Endotracheal intubation & ventilatory support if hypoxaemia or metabolic acidosis worsens or level of consciousness deteriorates.
  • Keep the head-end of the bed at 30-45° in mechanically ventilated patients.

WARNING:

Use NIV only if patient is awake and able to clear secretions and protect airway

In addition

  • If mechanical ventilation indicated, use lung protective strategies, i.e.
  • Tidal volume of 6-8 ml/kg of PBW
  • Plateau pressure <30mmHg
  • Use adequate PEEP
  • Use lung recruitment maneuvers and prone positioning in severe hypoxaemia (PaO2 /FiO2 <100)

*Antimicrobial

  therapy

  • Prompt oral or iv antibiotics to cover the most likely infection
  • Empiric broad spectrum antibiotic cover later guided by gram stain and culture and sensitivity reports.

 

  • Same
  • Procalcitonin levels to guide the duration of antibiotic therapy
  • Consider antifungal therapy if indicated in selective cases

Source control

  • Sought an anatomical diagnosis of infection
  • Incision & drainage of abscess within 12 hours

 

In addition

  • Consider surgical intervention for deep foci of infection

WARNING:

Consider removing
implants, devices, or central lines if suspected to be the source of infection

In addition

  • Consider CT guided diagnosis and drainage along with  surgical intervention

WARNING:

Promote use of oral chlorhexidine gluconate in ventilated patients as a form of oropharyngeal decontamination

Nutrition

  • Oral feeding as tolerated within 48 hours instead of only iv glucose
  • Consider enteral feeding within 48 hours of sepsis/severe sepsis as tolerated starting with 500Kcal/day

WARNING:
Avoid full caloric feed in the first week

  

WARNING:
Avoid TPN for first 7 days of onset of sepsis/severe sepsis

Others
  • Monitor and keep blood glucose level < 200 mg/dl

 

 

  • Protocolized approach to blood glucose management to target levels < 180 mg/dl with repeated point-of-care testing.

 

  • Stress ulcer prophylaxis with H2 Blockers or PPI
  • DVT Prophylaxis with twice daily UFH or compression stockings  in case of coagulopathy or low platelets

 

  • Target Hb 7-9 g/dl in the absence of bleeding and myocardial ischaemia or 10 g/dl if history of IHD

WARNING:

  • Do not use sodium bicarbonate as long as pH >7.20
  • Avoid FFP transfusion in the absence of bleeding to correct laboratory abnormalities

 

 

  • Protocolized approach to blood glucose management  to target levels < 180 mg/dl

 

  • Stress ulcer prophylaxis with PPI is preferred
  • DVT Prophylaxis with  daily LMWH & consider intermittent pneumatic compression device in case of coagulopathy or low platelets

 

  • Administer platelets if <10,000 and no risk of bleeding, <20,000/mm3 if there is significant risk of bleeding and < 50,000/mm3 if bleeding continues, or patient going for surgery or invasive procedure
  • Consider Renal Replacement Therapy (CRRT or HD)

 

WARNING:

  • Avoid use of neuromuscular blocking agents (NMBAs) in septic patient without ARDS.
  • Target specific titration endpoints for sedation in mechanically ventilated sepsis patients.

MAP = mean arterial pressure, CVP = central venous pressure, NIV = non-invasive ventilation, CPAP = continuous positive airway pressure, BIPAP = Bilevel positive airway pressure, ABG = arterial blood gas, PBW = predicted body weight, PEEP = positive end-expiratory pressure, CT= computerized tomography, TPN = total parenteral nutrition, PPI = proton pump inhibitors, DVT = deep vein thrombosis, UFH = unfractionated heparin, LMWH = low molecular weight heparin, IHD = ischaemic heart disease, FFP = fresh frozen plasma, CRRT = continuous renal replacement therapy, HD = haemodialysis, ARDS = acute respiratory distress syndrome.

                                                             GENERAL CONSIDERATIONS

 

Basic setup

Intermediate setup

Tertiary care setup

Hygiene

  • Observe Hand hygiene by soap & water
  • Observe Hand hygiene by alcohol hand rub.
  • Use disposable gloves while handling blood
  • Use sterile gloves , gown & face masks while doing sterile procedures
  • Use face mask if droplet infection suspected
  • In addition provide isolation for patients who are highly contagious

 

Monitoring

Clinically monitor pulse, blood pressure, temperature & mental state In addition

  • Use continuous non-invasive monitor for BP, SaO2, ECG,
  • Monitor GCS & hourly urine out put

In addition monitor invasive arterial blood pressure & CVP

Documentation

  • TPR
  • BP
  • Urine output
  • Level of consciousness (AVPU)
In addition document

  • HR, MAP, SaO2
  • GCS
  • Hourly intake and output
In addition document

  • Invasive pressures
  • CVP
  • Intra-abdominal pressure

Investigations

  • Hb/Hct
  • WBC
  • Platelet count
  • Urinalysis
  • RBS
In addition

  • UCE
  • Coagulation profile
  • ABG
  • LFT & albumen
  • Bilirubin
  • Gram staining
  • Malaria thick and thin smear
  • CRP
  • Cultures (blood, urine, tracheal, other body fluid)
In addition

  • Lactate
  • Procalcitonin,
  • Dengue serology
  • Malarial parasite

Multidisciplinary care

Take opinion from medicine and surgery Involve Anaesthesia Team In addition involve critical care team

  • Radiology
  • Sub-specialty

Estimate prognosis and limit therapy

  • Discuss goals of care and prognosis with family earlier.

 

  • Consider shifting the patient  to a hospital with  ICU facilities
  • Estimate prognosis by assessing degree of organ failure or SOFA-score

 

  • Discuss goals of care no later than 72 hours after admission
  • Estimate prognosis by assessing degree of organ dysfunction or APACHE II score

 

  • Limit or withdraw therapy in case of poor prognosis
  • Ethical consult

TPR = temperature, pulse rate, respiratory rate, BP = blood pressure, AVPU = awake, responds to verbal command, responds to painful stimulus, unresponsive, Hb = haemoglobin, Hct = haematocrit, RBS = random blood sugar, SaO2 = arterial oxygen saturation, ECG = electrocardiogram, GCS = Glasgow coma scale, UCE = urea-creatinine-electrolytes, LFT = liver function tests, CRP = C-reactive protein, SOFA-score = sequential organ failure assessment score, APACHE-score = acute physiology and chronic health evaluation score

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APPENDIX I

MEMBERS OF

SEPSIS GUIDELINES FOR PAKISTAN (SGP) COMMITTEE

Chair:

Professor Fazal Hameed Khan FCPS, EDIC

Professor of Anaesthesiology

Interim Chair Emergency Department

Aga Khan University, Karachi

Members:

  • Professor S. Tipu Sultan
    Patron PSCCM
    Professor of Anaesthesiology
    Sind Institute of Urology and Transplant
    Karachi
  • Professor Saeeda Haider
    Professor of Anaesthesiology
    The Indus Hospital
    Karachi
  • Professor Sadqa Aftab
    Professor of Anaesthesiology
    DUHS & Civil Hospital
    Karachi
  • Professor Roohina Baloch
    Chair Department of Anaesthesia
    Jinnah Post Graduate Medical Centre (JPMC)
    Karachi
  • Dr Ali bin Sarwar Zubairi
    Associate Professor & Section Head, Pulmonary & Critical Care Medicine
    Aga Khan University
    Karachi
  • Dr Javed Hussain
    Consultant Pulmonary & Critical Care Medicine
    South City Hospital
    NFT, Aga Khan University
    Karachi
  • Dr Anwar ul Haq
    Associate Professor & Director PICU
    Aga Khan University
    Karachi
  • Dr Madiha Hashmi
    President PSCCM
    Director SICU & Assistant Professor, Department of Anaesthesiology
    Aga Khan University
    Karachi
  • Dr Zahid Akhtar Rao
    Director SICU
    PNS Shifa Hospital
    Karachi
  • Dr Amin Khawaja
    National Institute of Cardiovascular Diseases (NICVD)
    Karachi
  • Dr Zunairah Rais
    Consultant Pulmonary & Critical Care Medicine
    Liaquat National Hospital (LNH)
    Karachi
  • Dr Syed Farjad Sultan
    Director ICU
    The Indus Hospital
    Karachi

Outside-Committee-Panel of Experts:

PUNJAB:

  • Brig Aslam Khan
    Professor of Medicine & Consultant Pulmonologist and Intensivist
    Military Hospital
    Rawalpindi.

BALUCHISTAN:

  • Prof. Amjad Ali
    Head of the Department
    Bolan Medical College
    Quetta

KPK:

  • Prof. Gohar Ali
    Head of the Department
    Lady Reading Hospital
    Peshawar

MMIDSP:

  • Prof Naseem Salahuddin
    Founder MMIDSP
    Infectious Diseases Consultant
    The Indus Hospital
    Karachi
  • Dr Faisal Sultan
    Consultant Physician, Internal Medicine & Infectious Disease
    Shaukat Khanum Memorial Cancer Hospital & Research Centre

PCS:

  • Prof Kamran Cheema
    President PCS
    Professor of Pulmonary Medicine
    Services Institute of Medical Sciences

 Appendix II

MMIDSP RECOMMENDATIONS FOR EMPIRIC ANTIBIOTIC THERAPY

Source of infection

Likely pathogen

Best empirical antibiotic

Urinary tract E. coli Carbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam
Genital tract E. coli, Enterococcus, S hemolyticus, Anaerobes Carbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam + vancomycin

Respiratory tract

(CAP)

S. pneumoniae, atypical pathogens Ceftriaxone +levofloxacin or clarithromycin

Respiratory tract

(HAP)

GPC, GNR, atypical Carbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam

+ levofloxacin or clarithromycin

Respiratory tract

(VAP)

GNR, MRSACarbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam + vancomycinIntra-abdominalGram negatives, anerobesCarbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam + vancomycinSSTI (necrotizing fasciitis)

S. aureus, Streptococci

anerobes

Amoxicilin/clavulanate or clindamycin+vancomycinBurn sepsisS. aureus, Streptococci, Pseudomonas, CandidaCarbapenem or Piperacillin –tazobactam orCefaperazone-sulbactam + vancomycinLine sepsisS. aureus, (MSSA, MRSA), PseudomonasCeftazidime  or amikacin+ vancomycinInfected deviceS. aureus, (MSSA, MRSA), PseudomonasCeftazidime  or amikacin+ vancomycinBacterial  meningitisS pneumonia, MeningococcusCeftriaxone + vancomycin + steroid

 

Appendix II

ANTIBIOTIC GROUPS, THEIR CHARACERISTICS AND USES

Class

Spectrum

Available preparations

Route of administration

Effective against

Not effective against

Carbapenem

Broad

Meroponem/imepenem / ertapenem

Intravenous

GPC, GNB, anaerobes

MRSA, VRE. Ertapenem ineffective against pseudomonas

B lactamase inhibitor

Broad

Piperacillin –tazobactam

Intravenous

GPC, GNB, anaerobes.

MRSA, VRE

3rd gen Cephalosporin

Broad

Cefaperazone-sulbactam

Intravenous

GPC, GNB, anaerobes.

MRSA, VRE

1st gen cephalosporin

Narrow

Cefazolin, Cephradine

Intravenous

Strept

MRSA, VRE, anaerobes

3rd gen Cephalosporin

Broad

Ceftriaxone

Intravenous

Strept, GNR

MRSA, VRE, anaerobes

3rd gen Cephalosporin

Broad

Ceftazidime

Intravenous

GNR, esp pseudom

MRSA, VRE, anaerobes

Glycopeptide

Narrow

Vancomycin

Intravenous

MRSA, enterococcus

GNR, anaerobes

Aminoglycoside

Narrow

Amikacin, Tobramycin, Gentamicin

Intravenous

GNR

Strept and Entero,, anaerobes

B lactamase inhibitor

Broad

Amoxicillin-clavulanate

Intravenous and oral

GPC, some GNR, anaerobes

E coli, enterobacteriacae

Fluoroquinolones

Broad

Levofloxacin

Intravenous and oral

GPC, atypical resp pathogens

Anaerobes

Macrolides

Narrow

Azithromycin, clarithromycin

Oral

Atypical resp pathogens

GNR, anaerobes

Lincosamide

Narrow

Clindamycin

Intravenous and oral

Strep, Staph (MSSA)

GNR

GPC gram positive cocci

GNR gram negative rods

MSSA methicillin sensitive Staph aureus

MRSA methicillin resistant Staph aureus