Dr hamada alsedawy sepsis and aki

1. SEPSIS&ACUTE KIDNEY INJURY
DR/HAMADA MOSTAFA
NEPHROLOGY SPECIALIST

2. CONTENTS
 SEPSIS
 LACTIC ACIDOSIS
 Recommended treatment paradigm for severe
sepsis patients
 Managing septic shock andAKI
 RenalprioritiesintheITU
 Urinary tract infection (UTI) in adults
 Sepsis and antimicrobials

3. A 63-year-old man develops AKI following knee surgery
and antibiotic use. The creatinine rose from 0.9 to 6.4
mg/dL.His urine output is <200 mL in 12-h, and his
serum [K+] is 5.5 mEq/L
Which one of the following is an absolute indication
for RRT?
A. Serum BUN 100 mg/dL
B. Serum [K+] >6 mEq/L with EKG changes
C. Serum pH <7.15
D. Urine output <200 mL for 12-h or anuria
E. All of the above

4. Absolute Relative
Metabolic abnormality BUN >100 mg/dL BUN >76 mg/dL
Hyperkalemia >6 mEq/L with EKG
changes
Hyperkalemia >6 mEq/L
Hypermagnesemia >8 mEq/L with anuria and
absent deep tendon reflexes
Hypermagnesemia >8
mEq/L
Dysnatremia
pH <7.15 >7.15
uremic signs and symptoms
such as encephalopathy,
pericarditis,
bleeding, neuropathy, and
myopathy
Lactic acidosis due to
metformin
Urine output Urine output <200 mL for
12-h or anuria
Anuria/oliguria RIFLE
class R
RIFLE class I
RIFLE class F
Fluid overload Diuretic-resistant Diuretic-responsive

5. AKI is associated with the following conditions?
A. Increased in-hospital mortality
B. Increased hospital stay and cost
C. Increased need for renal replacement therapy
(RRT)
D. Increased risk for progression to CKD and also
ESRD

6. patient had decreased urine output (<0.5 mL/kg/h) in 6-h, and her
creatinine is gradually increasing. Which one of the following
statements is TRUE regarding decreased urine output (oliguria) and
AKI in this patient?
A. Oliguria is defined as urine output <0.3 mL/kg/h for at least 24-h
by the Acute Dialysis Quality Initiative (ADQI)
group
B. Oliguria may be an expression of either normal response of the
kidneys to hypovolemia, or an expression of an underlying renal
disease
C. Approximately 69 % of ICU patients who developed AKI were
oliguric in one study
D. Oliguria in AKI patients is an independent predictor of mortality
E. All of the above

7. RIFLE and AKIN (Acute Kidney Injury Network)
defines oliguria <0.5 mL/kg/h for >6-h, <0.5 mL/kg/h
for >12-h, <0.3 mL/kg/h for >24-h.
Urine osmolality where maximal urine concentration
(osmolality >500 mOsm/kg H2O) is observed with
hypovolemia and isosthenuria (~300 >500 mOsm/kg
H2O) with diseased kidney.

8. Which one of the following statements is CORRECT regarding the
epidemiology of AKI in critically ill patients globally?
A. Severe AKI requiring ICU admissions occurs in 11 patients per
100,000 population per year
B. Using RIFLE criteria, one study reported the occurrence of AKI
in 36.1 % with 16.3 % in RIFLE-R category, 13.6 %
in RIFLE-I, and 6.3 % in RIFLE-F categories
C. Up to 20 % of bacteremic patients develop AKI, and increases to
50 % in patients with septic shock
D. The mortality in sepsis-related AKI is approximately 70 %
compared to approximately 45 % in non-sepsis-related
AKI patients
E. All of the above

9. The incidence of AKI is much higher in ICU than in
non-ICU patients.
Bacteremia/sepsis seems to be the underlying
etiology for most of the patients admitted to ICU.
It appears that the majority of patients admitted to
ICU with AKI had previous kidney dysfunction.

10. SEPSIS
• Sepsis is the leading cause of AKI in the intensive
care unit (ICU)
• Septic AKI is associated with high disease
severity scores, non-renal organ failure,
requirement for mechanical ventilation, need for
vasoactive drugs, extended lengths of ICU and
hospital stay, higher in-hospital mortality

11. Sepsis
Sepsis is defined as life-
threatening organ dysfunction
caused by a dysregulated host
response to infection.
• Organ dysfunction can be
identified as an acute change in
total SOFA score_2 points
consequent to the infection
(Sepsis-related Organ Failure Assessment)

12. Septic shock
Septic shock is a subset of sepsis in
which underlying circulatory and
cellular/metabolic abnormalities are
profound enough to substantially
increase mortality.
• Patients with septic shock can be
identified with a persisting hypotension
requiring vasopressors to
maintainMAP_65mmHg
a serum lactate level >2 mmol/L
(18mg/dL) despite adequate volume
resuscitation.

13. Definitions
Systemic inflammatory response syndrome (SIRS)
• Temperature >38.5 ° or <36.0 ° HR >90.RR >20, pCO 2
<4.2kPa, or the need for ventilation.WCC >12 or <4 (or blasts
>10%).
Sepsis—SIRS and:
• Positive cultures or focus of infection identified (e.g.
cellulitis/pneumonic changes on CXR).

14. Severe sepsis—sepsis + one of:
Skin mottling. Capillary refill ≥ 3s• UO <0.5mL/kg/h or
the need for dialysis.
Lactate >2mmol/L.• Altered mental status (or
abnormal EEG). Plt <100 or DIC. Acute lung injury
(ARDS). Impaired cardiac function.
Shock—severe sepsis + one of:MAP <60 (80 if known
hypertensive) after 40 – 60mL/kg 0.9% NaCl or20 –
30mL/kg colloid, does not respond to volume
resuscitation.

15. LACTICACIDOSIS
• Lactic acidosis is a common AG
acidosis, and it is by far the most
serious of all AG acidoses.
• Anaerobic metabolism of
glucose (glycolysis) occurs in the
extramitochondrial cytoplasm
• and produces pyruvate -pyruvate
• is quickly reduced by lactate
dehydrogenase to lactate,
• releasing energy,

16. Causes of a High Anion Gap Metabolic
Acidosis
A. Lactic Acidosis (Type A, Type B)
B. d-Lactic acidosis
C. Ketoacidosis
D. DKA
E. AKA
F. Starvation ketosis
G. Toxins/Drugs
H. Methanol
I. Ethylene glycol
J. Acetaminophen
K. Salicylate
L. Kidney Failure (with Severe Reductions in GFR)

17. Types and causes of lactic acidosis
Type A
1. Generalized seizure
2. Extreme exercise
3. Shock
4. Cardiac arrest
5. Low cardiac output
6. Severe anemia
7. Severe hypoxemia
8. Carbon monoxide poisoning

18. Type B lactic acidosis
 Sepsis Thiamine deficiency Uncontrolled diabetes mellitus
 Malignancy Hypoglycemia
 Drugs/toxins Ethanol Metformin Reverse transcriptase inhibitors
(e.g., Zidovudine)
 Salicylate Linezolid Propofol Niacin Isoniazid
 Nitroprusside Cyanide
 Catecholamines Cocaine Acetaminophen
 Streptozotocin Sorbitol/fructose Pheochromocytoma
 Malaria
 Inborn errors of metabolism
 Other Hepatic failure Respiratory or metabolic alkalosis
 Propylene glycol d-Lactic acidosis

19. Recommended treatment paradigm for severe sepsis
Patients
Early (hours 1–6)
◆ Make sepsis diagnosis.
◆ Send cultures from likely sites.
◆ Deliver antibiotics within 1 hour.
◆ Measure lactate.
◆ Obtain adequate access, including CVC for most patients.
◆ Ensure patient has adequate monitoring and nursing
staffing.
◆ Follow measures of perfusion (urine output, capillary refill,
pulse).
◆ Volume resuscitate.

20. Mid (hours 7–72)
◆ Monitor for signs of organ failure.
◆ Additional volume resuscitation if needed.
◆ Follow-up cultures: adjust antibiotics as needed.
◆ Minimize nosocomial complications: limit sedation, use
lung protective ventilation.
◆ Wean supportive therapies as feasible.
Late (hours > 73)
◆ Wean supportive therapies as feasible.
◆ Remove unnecessary devices.
◆ Minimize nosocomial complications: limit sedation, use
lung protective ventilation.
◆ Set endpoints for antibiotic therapy

21. Granting that the RIFLE and KDIGO criteria potentially
diagnose more ICU patients with severe sepsis or septic
shock as having AKI than the AKIN criteria, the prediction
ability for discerning in-hospital mortality was similar
between the three systems. Nonetheless, future prospective
studies enrolling a larger number of patients are still
warranted to better determine the sensitivity and prognostic
performance of these classifications in critically ill patients
with severe sepsis or septic shock

22. Managing septic shock andAKI
1) Antimicrobial therapy:
2) Fluid therapy
3) Vasopressor therapy:
4) Corticosteroids
5) Blood product administration
6) Glucose control

23. Fluid therapy
• Give an initial fluid challenge of ≥ 1000mL crystalloids (to
achieve a minimum of 30mL/kg in the first 4 – 6h).
• Continue incremental fluid boluses as long as there is
haemodynamic improvement, (e.g. CO, BP, heart rate) variables.
• Consider adding albumin to the initial fluid resuscitation regimen
if serum albumin is low.
• Avoid sodium bicarbonate therapy for the correction of
hypoperfusion-induced lactic acidaemia with pH ≥ 7.15

24. Antimicrobial therapy:
• Culture blood and other sites, and institute broad-spectrum
antibiotics within 1h.
• Antiviral and antifungal cover may be necessary, depending on the
clinical scenario.
• Image possible sites of infection as early as possible,
• Consider surgical treatment of localized source.
• In the event of d BP and/or lactate >4mmol/L, administer a
minimum bolus of 30mL/kg of crystalloid within 1h.
• Apply vasopressors for d BP unresponsive to initial fluid
resuscitation.
• Aim to maintain MAP ≥ 65mmHg.

25. During the first 6h of resuscitation, the goals
include all of the following:
CVP >8mmHg.MAP ≥ 65mmHg.UO ≥
0.5mL/kg/h.
 Central venous (superior vena cava) oxygen
saturation ≥ 70% (or mixed venous oxygen
saturation ≥ 65%).
 Aim to normalize serum lactate (a marker of
tissue hypoperfusion) as quickly as possible.

26. Vasopressor therapy:
•target an initial MAP of ≥ 65mmHg.
• Noradrenaline is first-line.
• Adrenaline can be added or
substituted if an additional agent is
•required to maintain BP.
•Vasopressin (0.03 units/min) can also
be added to, or substituted for,
noradrenaline.

27. Dopamine is an alternative to noradrenaline in selected
patients at low risk of arrhythmias who have low CO -/+low
heart rate.
Do not use low-dose dopamine for ‘renal protection ’ .
• Consider early placement of an arterial catheter in all
patients receiving vasopressor therapy.
• Add dobutamine to vasopressor therapy (if administered) in
the presence of: (i) myocardial dysfunction (as suggested by
elevated cardiac filling pressures and low CO); or
(ii) ongoing signs of hypoperfusion despite adequate
intravascular volume and MAP

28. Corticosteroids
• If patients require persistent high doses of
vasopressors for maintenance of adequate BP
despite adequate fluid resuscitation.
• Consider a continuous infusion of IV
hydrocortisone (200 – 300mg daily — no higher)
for a minimum of 5 days.
• Do not base the need for corticosteroid therapy on
ACTH stimulation testing.
• Hydrocortisone is now recommended alone,
rather than in combination with fludrocortisone.

29. Blood product administration
•Transfuse to maintain Hb >7.0g/dL
•Do not administer FFP to correct
laboratory clotting abnormalities unless
bleeding or planned invasive procedures.
•Antithrombin administration is no
longer recommended in the treatment of
severe sepsis.

30. Consider platelet administration if:
1. Counts are <5000/mm 3 (5 x 10 9 /L),
regardless of bleeding.
2. Counts are 5000 – 30,000/mm 3 (5 – 30 x 10 9
/L) and bleeding risk.
3. Surgery or invasive procedures is required:
counts ≥ 50,000/mm 3 (50 x 10 9 /L) are
recommended

31. Glucose control
• Hyperglycaemia impairs leucocyte function -/+less well
understood effects.
• Commence insulin when two consecutive blood glucose
levels are ≥ 10mmol/L (180mg/dL), and aim to keep blood
glucose levels ≤ 10mmol/L
• All patients receiving IV insulin should receive a glucose
calorie source.
• Blood glucose values should be monitored every 1 – 2h
until glucose values and infusion rates have stabilized and
then at least every 4h

32. Renal priorities in the ITU
• balanced crystalloid solutions are
increasingly recommended
• (hydroxyethylstarch has also previously
been implicated in i AKI).
• Avoid renoprotective strategies that lack
an evidence base, e.g. low-dose dopamine
is NOT recommended.

33. • There is no measurable superiority of either intermittent
HD (IHD) or CVVHDF, including outcomes for renal
recovery, in critically ill AKI patients, although
management of fluid balance is often easier with continuous
therapies
• High-dose CVVHF (aiming for an UF rate of
45mL/kg/min over 25mL/kg/min) does not demonstrably
improve outcomes.
• A larger delivered IHD dose (e.g. daily treatment) may
not improve outcomes but may have benefits over thrice
weekly HD interms of fluid and electrolyte management

34. High-dose RRT in sepsis
• High-dose CRRT means filtration volumes in the
range of 65mL/kg/h.
• Cytokine removal can also be achieved with IHD
and SLED, using special high-flux (i.e. large pore size)
membranes.
• Cytokine removal may not only be through UF, but
also via
adsorption on the filter membrane (potentially
increasing costs,
as the filter becomes cytokine-saturated and requires
regularly
changing).

37. A 24-year-old woman is admitted for fever with chills and
weakness. She is found to be hypotensive and tachycardic.
Blood cultures are positive for Staphylococcus aureus, and
the diagnosis of septic shock is made. There is no peripheral
edema. Based on the sensitivity, the patient is started on
vancomycin.
• Pertinent labs:
Na144 mEq/L Glucose 80 mg/dL K5.1 mEq/L Total protein 5.8 g/dL
Cl 88 mEq/L Albumin 2.0 g/d LHCO320 mEq/L Hemoglobin10 g/dL
BUN 30 mg/dL Hematocrit 30 % Creatinine 1.7 mg/dL Urinary Na 10
mEq/L
• Which one of the following fluids is APPROPRIATE for initial
resuscitation?
A. Packed red blood cells (pRBCs)
B. Half-normal saline
C. Normal saline
D. Ringer’s lactate
E. Albumin

38. • Rapid infusion of at least 1 L of saline is needed within an
hour and then at least 150–200 mL/h until BP, tissue
perfusion, and oxygen delivery are acceptable.
• Patients with septic shock can develop pulmonary edema
at pulmonary capillary wedge pressures <18 mmHg.
• Raising Hb >10 g/dL is not beneficial; therefore,
transfusion of pRBCs is not required However, the patient
needs transfusion of pRBCs once her Hb drops below 7
g/dL.

39. • Ringer’s lactate may be considered in the absence of lactic
acidosis and hyperkalemia. Because of low Cl, patient is less
prone to develop acute kidney injury, as compared with
normal saline. However, Ringer’s lactate and half-normal
saline may not be appropriate .
• Albumin may help restore BP and tissue perfusion, if BP
does not improve with substantial amount of normal saline
and the patient has trace edema.
• Vasopressors, in addition to albumin, may be required to
improve BP, tissue perfusion, and gas exchange. However,
albumin is not the initial choice of fluid resuscitation

40. Urinary tract infection (UTI)
in adults
•1-Acute uncomplicated cystitis in
young women
•2-Recurrent acute uncomplicated
cystitis in young women
•3-Acute uncomplicated pyelonephritis
in young women
•4-Asymptomatic bacteriuria

41. 5-Acute uncomplicated cystitis in adults with a following
condition
• suggesting possible occult renal or prostatic
involvement but without other known complicating
factors:
• Male sex
• Elderly
• Pregnancy
• Diabetes mellitus
• Recent urinary tract instrumentation
• Childhood urinary tract infection
• Symptoms for more than 7 days at presentation

42. 6-Complicated urinary tract infection
• Obstruction or other structural factor:urolithiasis,malignancies,
ureteral and urethral strictures, bladderdiverticula, renal cysts,
fistulas, ileal conduits, other urinary diversions
• Functional abnormality: neurogenic bladder, vesicoureteral
reflux
• Foreign bodies: indwelling catheter, ureteral stent,
nephrostomy tube
• Other conditions: renal failure, renal transplantation,
immunosuppression, multidrug-resistant uropathogens,
• health care–associated (includes hospital-acquired/nosocomial
place) infection, prostatitis-related infection,upper tract infection
in an adult other than a healthy youngwoman, other functional or
anatomic abnormality of urinary tract)

43. Sepsis and antimicrobials
• reduce hospital-related infections,such as MRSA and C.
diffi cile , and help to prevent antibiotic resistance.
• Always record indication and intended antibiotic duration
or review date.
• IV antibiotics should be switched to oral equivalents after
48h if T <38 * C for 48h, patient is clinically improving, a
suitable oral agent is available, and there is no evidence of
malabsorption, gastric stasis, or vomiting.
• There are exceptions (e.g. PD peritonitis, endocarditis,
meningitis

44. High doses of B -lactam
antibiotics
accumulate and cause neurological
sequelae, including confusion, agitation,
and seizures in advanced CKD,
including dialysis patients

45. Vancomycin
vancomycin-induced AKI or nephrotoxicity, which one of the following
statements is FALSE?
• A. Vancomycin is excreted mostly by the kidneys, and dose adjustment is
necessary in renal failure
• B. The incidence of nephrotoxicity varies between 0 and 7 % when
vancomycin used alone
• C. There is no increased nephrotoxicity when vancomycin is used with
aminoglycosides
• D. The incidence of nephrotoxity increases with increasing trough levels of
vancomycin
• E. Vancomycin-induced nephrotoxicity is mediated by increased oxidative
stress

46. • The answer is C
• All of the above statements are correct
except C. Indeed, a meta-analysis reported
13.3%increase in nephrotoxicity in
combination therapy compared to
vancomycin therapy alone. Thus, C is false.

47. Aminoglycosides
• are nephrotoxic. A vicious cycle of rising drug
levels and worsening renal function can (and often
does) result.
• Several factors increase risk of both nephrotoxicity
and ototoxicity:
prolonged treatment, dehydration, concomitant
diuretic use, obstructive jaundice, hypokalaemia, and
hypomagnesaemia.
• Dose adjustments aim to achieve peak plasma levels
that are bactericidal whilst permitting low trough
levels that avoid toxicity.

48. risk factors forAG-inducedAKI.
• AGs cause nonoliguric AKI.
• Volume resuscitation with normal saline, and single daily
intravenous dose of AG can reduce the incidence of AG-
induced AKI.
• Continuous infusion and multiple (frequent) daily doses
should be avoided, as these practices can cause
accumulation of AG, particularly gentamicin, in the renal
cortex, and can take several days to wash out the drug out of
the tissue with appropriate volume replacement.

50. THANKYOU