703R. Chawla and S. Todi (eds.), ICU Protocols: A stepwise approach, DOI 10.1007/978-81-322-0535-7_88, © Springer India 2012

A 2-year-old boy was brought to the emergency department with lethargy, poor feeding, fever for the past 24 h, cold extremities, mild respiratory distress for the past 3 h, and no urine output for the past 8 h. He was lethargic but arousable. His rectal temperature was 104°F, with heart rate 170/min, blood pressure 60 mmHg, respiratory rate 45 breaths/min, and SpO

2 92% at room air. Capillary re fi ll time

was 5 s, and extremities were cold with palpable but feeble pulses .

P. Khilnani , M.D., F.C.C.M. (*) Pediatric Critical Care and Pulmonology , BL Kapur Memorial Hospital , New Delhi , India e-mail: khilnanip@hotmail.com

88 Severe Sepsis and Septic Shock

Praveen Khilnani

Severe sepsis and septic shock involve clinical SIRS (systemic in fl ammatory response syndrome) with suspected or proven infection (blood culture not always positive) with cardiovascular involvement and dysfunction (septic shock) or multi-ple organ involvement (severe sepsis with multiple organ dysfunction syndrome). This chapter describes the step-by-step management of severe sepsis and septic shock.

Step 1: Initial resuscitation This includes fast recognition and action done almost simultaneously. • Shock should be clinically diagnosed before hypotension occurs by clinical • signs, which include the following:

Hypothermia or hyperthermia – Altered mental status – Peripheral vasodilation (warm shock) or vasoconstriction with capillary re fi ll –more than 2 s (cold shock) Tachycardia – Tachypnea out of range for age and level of fever or anxiety –

704 P. Khilnani

Zero minutes Recognize decreased mental status and perfusion Maintain and establish vascular access—use intraosseous if IV fails in 90 s 5–15 min : Push 20 mL/kg normal saline/colloid × 3 up to 60 mL/kg Assess between each push Correct hypoglycemia and hypocalcemia

There should be no time wasted in gaining access. If access is not easily obtained • in about 90 s, the interosseous route is a must, as almost everything can go in by that route including inotropes. Because mortality goes up with delay in time to inotrope drug use, now it is rec-• ommended to use the peripheral line for inotropes—dopamine and dobutamine (not vasopressors)—until central access is attained. • Optimizing fl uids in the fi rst 15 min or as soon as possible : Pediatric septic shock is associated with severe intravascular volume depletion, and children frequently respond well to aggressive volume resuscitation. The continued emphasis is on the fi rst-hour fl uid resuscitation, and appropriate • inotrope drug therapy is directed to achieve the following goals:

Reducing heart rate to the threshold level for age – Getting peripheral pulse to match central pulse volume – Improving mentation – Improving urine output to at least 1 mL/kg/h – Reducing clot retraction time to less than 3 s. –

This assessment for quick check for overload is done after each bolus of fl uid. Rapid expansion of the liver span • Rales and increased work of breathing • Enlargement of the cardiac silhouette on chest X-ray • Drop in SPO •

2

Step 2: Manage 15-min fl uid-refractory shock Establish central venous access. • Start dopamine 10 mcg/kg/min. • Establish arterial access. • Continue maintenance fl uids 4 mL/kg/h and boluses of .9% normal saline/colloid • as needed. Thirty to sixty minutes have passed— fl uid-refractory, dopamine-resistant shock. •

Scenarios 1. When pediatric patients are normotensive with a low cardiac output (CO) and

high systemic vascular resistance (SVR), initial treatment of fl uid-refractory patients consists of the use of an inotropic agent such as dobutamine. Dopamine at a dose of 10–15 m /kg/min should be administered at this time.

70588 Severe Sepsis and Septic Shock

However, fl uid-refractory, dopamine-resistant shock is an important de fi ning step as the mortality changes when the patient fails to respond to fl uids and dopamine.

2. When pediatric patients are hypotensive with a low CO and high SVR (cold shock), EPI (epinephrine) is started at a dose of 0.1 m g/kg and titrated to effect. When BP improves, an inodilator (dobutamine, milrinone, and nitroglycerine) is added to improve tissue perfusion. This can be done using the same clinical parameters described above or additional laboratory data such as base excess of more than 5 or increasing lactate levels.

3. When pediatric patients are hypotensive with a high CO and low SVR (warm shock), then norepinephrine is the vasopressor of choice. Since the pulse pres-sure is wide and diastolic pressures are usually low, the need is to increase the mean arterial pressure (MAP). Here, a vasodilator can be added.

There is no magic formula for inotrope or fl uid titration. The guidelines are there to give a framework for initiating and adding drugs based on clinical examining and parameter readings of central venous pressure (CVP), BP, etc. Many children by now may be on more than three agents including vasopressors and vasodilators.

Step 3: Early goal-directed therapy It restores the balance between delivery and demand quickly by manipulating • preload, afterload, and contractility using fl uids, inotropes, and vasodilators to enhance delivery and PRBCs to deliver more oxygen by increasing O

2 content

(Table 88.1 ). All four goals to be met for success •

Step 4: Give antibiotics within the fi rst hour and control the source An increased mortality rate due to delay in the administration of an appropriate • antibiotic has been clearly shown in several pediatric and adult studies. Therefore, every attempt should be made to get appropriate cultures earlier, but this should not hold up the administration of the drug. The choice should be on the basis of the site of infection and local patterns. • A broad-spectrum antibiotic like a third-generation cephalosporin should be used. De-escalate antibiotics once the culture results are available. Along with this, there must be an active search for a source of infection, and • immediate action for source control should be taken wherever possible.

Step 5: Mechanical ventilation and sedation There are many reasons to ventilate patients with septic shock. This step should • be considered in any patient who is not rapidly stabilized with fl uid resuscitation and peripherally administered inotropes.

1. Normal MAP (>60 mmHg) 2. Mixed venous saturation >70% 3. Urine output >1 mL/kg/h 4. CVP >8–12 cm H

2 O

Table 88.1 Early goal-directed therapy

706 P. Khilnani

Step 6: Give steroids If a child is at risk of absolute adrenal insuf fi ciency (e.g., purpura fulminans, • congenital adrenal hyperplasia, prior recent steroid exposure as in asthma, or nephrotic syndrome) and remains in shock despite epinephrine or norepineph-rine infusion, fl uids and inotropes are optimized for an hour (catecholamine-resistant shock) and then hydrocortisone can be administered. Hydrocortisone may be administered as an intermittent or continuous infusion at • a dosage of 50 mg/m 2 /day (2 mg/kg 6-hourly) till hemodynamic stability is achieved.

Step 7: Glucose control Glucose-containing fl uids D5 or D10 along with insulin should be used for main-• tenance, and insulin is titrated to keep blood glucose between 100 and 150 mg/dL. This prevents catabolism as well as the ill effects of hyperglycemia. Tight glucose control leads to hypoglycemia and this can be brain damaging, so • avoid this and maintain higher glucose value. Hyperglycemia should not be treated by reducing fl uid concentrations to glucose-free fl uids and removing insulin as there is poor glucose utilization and insulin is needed.

Summary of guidelines for pediatric septic shock management in resource-limited environment

Immediate recognition of shock state from decreased perfusion state and altered • mental status. Airway, breathing, and circulation approach with high- fl ow O •

2 .

Rapid intraosseous access immediately, if IV is not available. • Up to 60 mL/kg isotonic nonglucose-containing fl uid can be given for 0–15 min. • Clinical evaluation of improvement of shock by decreasing heart rate, clot retrac-• tion time less than 2 s, improved mental status, improved peripheral pulse and central pulse, improved urine output, warmer extremities, and MAP more than 60 mmHg (age-related values). Evaluate for fl uid overload. • Rapid decision to start dopamine/dobutamine by the peripheral line, not wait for • the central line. Start appropriate antibiotics in fi rst hour. • Continue fl uid boluses as needed throughout the process—in the fi rst few hours—• and continue maintenance fl uids. Mechanical ventilation with sedation and analgesia. • If fl uid-refractory, dopamine-resistant shock, insert CVP and arterial line. • Epinephrine for cold shock, norepinephrine for warm shock ± vasodilators. • Steroids for catecholamine-resistant shock at 2 mg/kg/day q8. • Early goal-directed therapy with ScVO •

2 more than 70%, hemoglobin 10 g/dL,

CVP 8–12 cm H 2 O, and MAP more than 60 mmHg.

Source control as soon as possible. • Glucose control with insulin if needed (<150 mg/dL). •

70788 Severe Sepsis and Septic Shock

Suggested Reading

1. Khilnani P, Singhi S, Lodha R, et al. Pediatric sepsis guidelines: summary for resource- limited countries. Indian J Crit Care Med. 2010;14(1):41–52.

Pediatric sepsis guidelines are presented in text and fl ow chart format, keeping resource limita-tions in mind for countries such as India and Africa.

2. Brierley J, Carcillo JA. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med. 2009;37:666–88.

The 2007 update continues to emphasize early use of age-speci fi c therapies to attain time-sensitive goals, speci fi cally recommending (1) fi rst-hour fl uid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary re fi ll £ 2 s and (2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3–6.0 L/min/m.

3. Zimmerman J, Barker R, Cantini C. Effect of adjunctive corticosteroids on clinical outcomes in pediatric sepsis syndrome. Abstr 461. Crit Care Med. 2006;34(Suppl 12):A129.

4. Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics. 112:793–99.

Early recognition and aggressive resuscitation of pediatric and neonatal septic shock by com-munity physicians can save lives.

5. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–77.

Early goal-directed therapy provides signi fi cant bene fi ts with respect to outcome in patients with severe sepsis and septic shock .