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Marie Holowaychuk, DVM, DACVECC Critical Care Vet Consulting

www.criticalcarevet.ca

Stop Sepsis! Management of Critically Ill Septic Dogs

Introduction

Justine A. Lee, DVM, DACVECC, DABT

CEO, VETgirl

Garret Pachtinger, VMD, DACVECC

COO, VETgirl

Introduction Marie Holowaychuk, DVM,

DACVECC

Critical Care Vet Consulting

www.criticalcarevet.ca

Introduction

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Outline !  Human and canine statistics !  Categories and clinical signs !  Etiology !  Clinicopathologic findings !  Biomarkers !  Diagnostic imaging !  Confirmation of sepsis !  Treatment !  Prognosis

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Sepsis Statistics - Humans !  More than 18 million cases of sepsis are diagnosed

worldwide each year !  Leading cause of death in non-coronary ICUs !  Approximately 1,400 people die from sepsis each

day !  The number of sepsis cases is expected to grow as

the population ages !  Mortality rates are high (30-60%) !  A 25% reduction in mortality would save over 1

million people annually

Sepsis Statistics – Dogs !  Incidence/prevalence not specifically studied

!  4% of dogs admitted to ICU primarily for sepsis (Hayes G et al. J Vet Intern Med 2010)

!  Mortality rates are similar to those in people: !  50% (de Laforcade A et al. J Vet Intern Med 2003) !  53% (Burkitt J et al. J Vet Intern Med 2007) !  47% (Kenney E et al. J Am Vet Med Assoc 2010) !  36% (Cortellini S et al. J Vet Emerg Crit Care 2014)

!  No change in mortality in dogs with septic peritonitis during 1998-1993 (64%) vs. 1997-2003 (57%) (Bentley A et al. J Vet Emerg Crit Care 2007)

Sepsis – Definitions !  Documented or suspected infection with

concurrent clinical criteria for systemic inflammation

Systemic Inflammatory Response Syndrome (SIRS)

People Dogs !  Temperature > 100.4oF or < 96.8oF

(> 38.3oC or < 36oC) !  Heart rate > 90 bpm !  Tachypnea !  Altered mental status !  WBC count > 12,000 or < 4,000/µL

(> 12.0 or < 4.0 ×109/L) !  Bands > 10% of WBC count !  Hyperglycemia (BG > 140 mg/dL [>

7.7 mmol/L]) in the absence of diabetes

!  Elevated C-reactive protein or procalcitonin

!  Temperature > 102.6oF or < 100.6oF (> 39.2oC or < 38.1oC)

!  Heart rate > 120 bpm !  Respiratory rate > 20

breaths/min !  WBC count > 16,000 or <

6,000/µL (> 16.0 or < 6.0 ×109/L)

!  Bands > 3% of WBC count

> 2 signs is consistent with SIRS

Severe Sepsis !  Sepsis associated with:

! Organ dysfunction ! PaO2/FIO2 < 300 mmHg ! Acute oliguria or creatinine increase > 0.5 mg/dL (>

44 µmol/L) ! Coagulation abnormalities (aPTT > 60 sec) or

platelets < 100,000/µL (< 100 ×109/L) ! Total bilirubin > 4 mg/dL (> 70 µmol/L)

! Hypoperfusion ! Lactate > 2.0 mmol/L

! Hypotension ! Systolic BP < 90 mmHg, mean BP < 70 mmHg, or

decrease in systolic BP > 40 mmHg

Septic Shock !  Persistent hypotension despite adequate fluid

resuscitation

!  Catecholamine-resistant septic shock = persistent hypotension despite adequate fluid resuscitation and vasopressor therapy

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Etiology !  Abdominal

!  Leakage of GI contents !  Penetrating trauma !  Pancreatitis/abscess !  Liver abscess/hepatitis !  Ruptured infected gall

bladder !  Splenic abscess !  Mesenteric lymph node

abscess !  Umbilical abscess

!  Pulmonary !  Pyothorax !  Pneumonia

!  Urogenital !  Pyelonephritis !  Pyometra !  Prostatic abscess

!  Dermatologic !  Infected wounds !  Cellulitis

!  Musculoskeletal !  Osteomyelitis !  Myositis

!  Cardiovascular !  Endocarditis !  Pericarditis !  Bacteremia

Clinical Signs: Related to Underlying Etiology

!  Abdominal ! Pain ! Distension

!  Pulmonary !  Increased respiratory

effort ! Pulmonary crackles ! Dull lung/heart sounds

!  Cardiovascular ! Heart murmur ! Muffled lung sounds

!  Urogenital ! Preputial or vaginal

discharge ! Abdominal pain

!  Dermatologic ! Wounds ! Swelling, redness ! Pain

!  Musculoskeletal ! Lameness ! Pain

Clinical Signs: Sepsis and Severe Sepsis

!  Fever !  Tachycardia !  Tachypnea !  Lethargy and dull

mentation !  Injected mucous

membranes !  < 1 sec capillary refill

time !  Bounding pulses !  Dehydration

Clinical Signs: Septic Shock

!  Tachycardia or bradycardia

!  Tachypnea !  Variable body

temperature !  Stuporous mentation !  Pale or grey mucous

membranes !  > 2 sec capillary refill

time !  Weak or absent pulses

Minimum Database !  Venous blood gas

and/or lactate !  Complete blood count !  Biochemistry profile !  Urinalysis !  Clotting profile

! PT, aPTT ! +/- fibrinogen ! +/- D-dimers, FDPs

Laboratory Findings !  CBC:

! Leukocytosis or leukopenia

! Left shift ! Toxic change ! Thrombocytopenia

!  Biochemistry: !  Increased liver

enzymes !  Increased total

bilirubin ! Azotemia

!  Thyroid profile: ! Decreased total T4 ! Normal free T4

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Laboratory Findings !  Clotting Profile:

! Prolonged PT/aPTT !  Increased D-dimers or

FDPs ! Decreased fibrinogen

!  Urinalysis: ! Variable USG ! Active urine sediment

!  Blood gas: ! Metabolic acidosis ! Elevated lactate

Diagnostic Imaging !  Thoracic and abdominal radiographs !  Thoracic and abdominal FAST !  +/- comprehensive abdominal ultrasound !  +/- echocardiography !  +/- CT scan or other advanced imaging

Thoracic Radiographs !  Interstitial to alveolar

pulmonary infiltrate !  Pleural fissure lines

Abdominal Radiographs !  Mass or foreign body !  Intestinal gas

distension or ileus !  Decreased serosal

detail !  Free peritoneal gas

Thoracic and Abdominal FAST !  Free fluid

Focused Assessment using Sonography for Trauma (FAST)

! Simple and rapid ultrasound exam ! Used only to detect free fluid ! No assessment of echogenicity of organs ! Performed in < 5 minutes ! Can be used with a scoring system (score 0 to 4

out of 4) to evaluate for fluid in 4 areas

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Abdominal FAST

!  Right lateral recumbency

!  Assess for fluid (anechoic area around organs) in the following locations: ! Diaphragmatico-hepatic (DH): caudal to xiphoid ! Spleno-renal (SR): left flank ! Cysto-colic (CC): midline over urinary bladder ! Hepato-renal (HR): right flank (dependent)

Abdominal FAST !  DH and CC views most likely to reveal fluid in patients

with lower fluid scores !  Visualize the urinary and gall bladders !  Perform serial exams and fluid scores to monitor for

increases in fluid !  Identify a pocket of fluid for sampling

Thoracic FAST !  Use to rule out pleural or pericardial effusion !  Can help to identify a pocket of fluid for sampling !  Depending on expertise, can also assess heart for

sepsis-related changes: ! Contractility ! Volume status

Comprehensive Abdominal Ultrasound

!  Intestinal foreign body !  Mass or cyst !  Fluid-filled uterus !  Peritoneal effusion !  Diseased

parenchymal organ !  Abnormal gall bladder !  Distended intestines !  Free peritoneal gas

Echocardiography !  Source of sepsis:

! Endocarditis ! Pericardial effusion ! Pericardial thickening

!  Cardiovascular dysfunction: ! Decreased

fractional shortening ! Decreased ejection

fraction !  Increased end-

systolic volume

CT scan

!  Mass !  Abscess !  Foreign body

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Infection Documented Suspected

!  Positive culture ! Urine ! Blood ! Fluid ! Tissue

!  Cytologic evidence of bacteria

!  Positive gram stain !  Positive PCR

!  Leakage of GI contents

!  Ruptured abscess !  Abdominal fluid

lactate/glucose measurements

!  Biomarkers

Sepsis Biomarkers !  Measurable diagnostic or

prognostic indicator of sepsis

!  Heavily studied in human medicine

!  More studies recently involving dogs

!  Further investigation needed before application in clinical practice

!  Examples: ! Lactate ! C-reactive protein ! Serum amyloid A ! NT-proCNP ! HMGB-1 ! Nitrate/nitrite !  Ionized calcium ! von Willebrand

factor ! Cytokines ! Procalcitonin

Samples for Analysis !  Urine !  Blood !  Fluid

! Airway ! Abdominal !  Joint ! Pleural ! Wound/abscess

Urine !  Sampling techniques:

! Cystocentesis ! Sterile catheterization

!  Collect sample for: ! Sediment analysis ! Aerobic bacterial

culture and sensitivity

Blood !  Sampling techniques:

! Sterile venipuncture ! Sampling from indwelling

catheter !  If concerns re: catheter-

associated infection

!  Collect sample for: ! Aerobic and

anaerobic bacterial culture and sensitivity

! PCR analysis

Blood Culture Limitations

Limitations Solution !  Contamination !  Poor timing of

collection !  Insufficient blood

volume cultured !  Antibiotics given

before blood collection

!  Sample multiple sites and consider discard sample

!  Sample 1 hour apart if patient stable

!  Collected blood for 2-3 culture tubes (3-10 mL each)

!  Collect samples early !  Use resin-based culture

media to neutralize antibiotics

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Blood Culture Supplies !  Alcohol swabs !  Sterile gloves !  Surgical scrub !  Butterfly needle !  20G needle !  6-12 mL syringe !  Blood culture bottles

! Pediatric (3 mL) ! Adult (8-20 mL)

Blood Culture Technique 1.  Clip and prep the venipuncture site 2.  Don sterile gloves 3.  Perform venipuncture with butterfly needle 4.  Collect the desired blood volume 5.  Swab culture bottle with alcohol 6.  Exchange butterfly needle for 20G needle 7.  Instill blood into the culture bottle 8.  Store at room temperature until transfer to lab 9.  Repeat procedure at 1-2 other sites

!  Preferably 1 hour apart !  Can do simultaneously to expedite process

Blood Culture Interpretation !  Results can take up to 5-7 days

!  Known contaminants are disregarded: ! Coagulase-negative Staphylococcus strains ! Propionibacterium strains ! Diphtheroids (primarily Corynebacterium sp) ! Bacillus sp

!  True bacteremia is indicated by: ! Same bacteria species/strain cultured from > 1 site ! Staphylococcus aureus, Streptococcus sp., and

enterobacteriaceae

Blood Culture vs. PCR

The Vet J 2013;198:714-716

Airway Fluid !  Sampling techniques:

! Transtracheal wash ! Endotracheal wash/

brush ! Bronchoalveolar lavage/

brush

!  Collect sample for: ! Cytology ! Gram stain ! Aerobic bacterial

culture and sensitivity

Other Pulmonary Samples !  Sampling techniques:

! Deep oral (pharyngeal) swab (adult dogs – hospital-acquired pneumonia)

! Thoracocentesis ! Transthoracic pulmonary

aspirate

!  Collect sample for: ! Cytology ! Gram stain ! Aerobic bacterial

culture and sensitivity

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Abdominal Fluid !  Sampling techniques:

! Blind abdominocentesis ! Ultrasound-guided

abdominocentesis ! Standing = not

recommended (high risk of splenic puncture)

!  Collect sample for: ! Fluid analysis ! Cytology ! Gram stain ! Aerobic and

anaerobic bacterial culture and sensitivity

! Fluid:blood glucose and lactate difference

Blind Abdominocentesis !  Patient in right lateral recumbency !  Clip and perform sterile prep. of the area around the

umbilicus !  Ideal site: 2-3 cm caudal to the umbilicus and 2-3 cm

from midline (dependent region)

Four Quadrant Abdominocentesis !  Closed technique (syringe attached) is recommended !  Open technique can introduce air into abdominal

cavity affecting diagnostic imaging interpretation

Pneumoperitoneum

Four Quadrant Abdominocentesis !  Repeat blind technique in 4 locations

! 2-3 cm cranial and caudal to umbilicus and 2-3 cm lateral to baseline

Ultrasound-Guided Abdominocentesis !  Ultrasound used to find a “pocket” of fluid (i.e.,

anechoic region) !  Perform blind technique in region of “pocket” or

visualize needle advancing into pocket

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Abdominocentesis Technique !  3-6 mL syringe and 20-22G

needle !  Advanced perpendicular to

the skin !  Once through the skin, apply

suction !  Advance through SQ tissue

and abdominal wall with constant or intermittent suction

!  Fluid should enter syringe as soon as abdominal wall penetrated

Sample Collection Supplies 1.  EDTA (lavender top) tube 2.  Serum (red top) tube 3.  Additional sterile (red top or other) tubes or swabs 4.  Slides (if not enough fluid to put into tubes)

In-house Analysis: EDTA tubes !  Performed at/near room

temperature !  PCV and total solids (TS)

! Dilution of PCV if small sample

! Turbid samples centrifuged and TS measured on supernatant

!  Prepare smears for cytology (Diff-Quik) ! Direct if flocculent/turbid

samples ! Centrifuge and smear

sediment if clear/hazy

In-house Analysis: Serum tubes !  Compare abdominal fluid to blood sample

measurements !  Delay in sample processing can affect the results

! Glucose ↓ and lactate ↑

Lactate and Glucose Measurements !  Septic peritonitis suspected if:

! Abdominal fluid glucose > 20 mg/dL (> 1.1 mmol/L) lower than the peripheral BG

! Abdominal fluid lactate > 1.5 mmol/L higher than the peripheral blood lactate

! Fluid lactate > 2.5 mmol/L

!  Only reliable in dogs

Send-out Analysis: EDTA tubes !  Total nucleated cell count (TNCC) !  Cytology (microscopic review by clinical pathologist) !  Smears should be prepared at the time of sample

collection to submit with the fluid ! Reduces artifactual changes in cell morphology

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Pure Transudate! Modified Transudate!

Exudate! Chyle!

Color! Transparent – straw yellow$

Transparent – yellow – reddish

Yellow – red Viscous!

White – pink Cloudy$

Protein (g/L)! ≤ 25$ 25-75 ≥ 30! ≥ 25$

Total nucleated cell count (TNCC) /µL (× 109/L)!

≤ 1,500 $(≤ 1.5) $

1,500-7,000 (1.5 – 7.0) $

> 7,000!(> 7.0)!

500-20,000 (0.5 – 20.0)$

Predominant cells!

Rare monocytes and mesothelial cells$

Variable (monocytes, lymphocytes)

Neutrophils (PMNs) (possibly degenerative)!

Mature lymphocytes, PMNs, macrophages$

Common causes!

Hypoalbuminemia, cirrhosis, portal hypertension$

Heart failure, vasculitis, diaphragmatic hernia, portal hypertension$

Bacterial or fungal infection, neoplasia, FIP, pancreatitis!

Trauma, lymphatic obstruction, heart failure, idiopathic$

Send-out Analysis: Serum or culture tubes

!  Stored or submitted for aerobic and/or anaerobic bacterial, mycoplasma, or fungal cultures

!  Anaerobic cultures should not be refrigerated and ideally submitted within 24 hours

!  Culture results take at least 48-72 hours !  EDTA is bacteriostic – do not submit lavender top

tubes for culture!

Sabrina – 9 month old Bull Mastiff !  T = 102.6oF (39.2oC) !  P = 160 bpm !  R = 40 breaths/min !  MM = dark pink !  CRT = 1 sec !  BP = 107/63 (71) mmHg !  Depressed mentation !  Painful abdomen !  Oozing serosanguinous

fluid from incision

Presented for lethargy and inappetence 3 days after enterotomy for a GI FB removal

Lab work !  pH = 7.339 !  pCO2 = 45.8 mmHg !  HCO3 = 23.3 mmol/L !  BE = -1.4 mmol/L !  Lactate = 2.5 mmol/L

!  PCV = 48% !  TS = 5.2 g/dL (52 g/L) !  BG = 90 mg/dL (5.0 mmol/L)

!  Na = 133 mmol/L !  K = 4.0 mmol/L !  Cl = 103 mmol/L !  iCa = 1.14 mmol/L

Diagnostic Imaging !  Radiographs:

! Loss of abdominal serosal detail

!  FAST exam: ! Moderate

abdominal fluid ! AFS = 3/4

Diagnosis of Sepsis !  Abdominocentesis:

! Serosanguinous cloudy fluid

!  Fluid analysis: ! Exudate: ! TNCC = 16,500/µL (16.5

x 109/L) ! TS = 3.5 g/dL (35 g/L) ! Septic suppurative

inflammation ! Sample submitted for

aerobic/anaerobic culture

Image courtesy of Darren Wood

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Glucose/Lactate Measurements !  Peripheral blood:

!  Glucose = 90 mg/dL (5.0 mmol/L)

!  Lactate = 2.5 mmol/L

!  Abdominal fluid: !  Glucose = 1.8 mg/dL

(0.1 mmol/L) !  Lactate = 12.5 mmol/L

!  Abdominal fluid-blood: !  Glucose = - 88 mg/dL

(- 4.9 mmol/L) !  Lactate = 10.0 mmol/L

Diagnosis = septic peritonitis likely secondary to leakage from enterotomy site

!  Quality of evidence

!  Strength of recommendation

Grade A High Grade B Moderate Grade C Low Grade D Very Low

Grade 1 Strong

Grade 2 Weak

Initial Resuscitation & Infection Management

!  Initial Resuscitation (Grade 1C) ! Fluid resuscitation of patients with sepsis-induced

tissue hypoperfusion !  Diagnosis of Sepsis (Grade 1C)

! Obtain samples for cytology and/or culture !  Imaging studies to confirm potential source of infection

!  Antimicrobial Therapy (Grade 1B) ! Administration of broad-spectrum IV antibiotics within

the first hour of recognition of severe sepsis or septic shock

!  Source Control (Grade 1C-D) !  Intervention within the first 12 hours after source

identified

Fluid Resuscitation !  Place an IV catheter

! Cephalic or saphenous initially

!  Administer isotonic crystalloid boluses ! LRS, Plasmalyte-A, Plasmalyte-148, Normosol-R ! 20-25 mL/kg IV over 15 minutes ! Re-assess perfusion parameters ! Continue until perfusion restored up to 80-100 mL/

kg

Response to Fluid Resuscitation Parameter Target

Heart rate 80-140 bpm

Resp. rate 18-24/min

Pulses Palpable femoral & dorsal pedal Systolic BP 100-120 mmHg

Mean BP 70-80 mmHg

Lactate < 2 mmol/L

Urine output > 1 mL/kg/hour

Mentation Responsive

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!  Prospective observational study !  30 dogs admitted for untreated hypovolemic or septic

shock !  Fluid resuscitated to normalization of PE perfusion

parameters and Doppler/systolic BP > 90 mmHg !  Then placement of central venous catheter and

measurement of ScvO2

!  Dogs stratified to > or < 70% measurements post-resuscitation

!  All dogs had normalization of traditional perfusion parameters (HR, BP, PE)

!  Median crystalloid dose: 63 mL/kg !  Median HES dose: 4.8 mL/kg !  Median duration of resuscitation was 3 hours !  1/3 of dogs had ScvO2 < 70% and were more likely to

have lactate > 2 mmol/L ! No difference in fluid volume delivered to groups

!  Suggests persistent oxygen debt despite normalization of standard perfusion parameters

Broad-Spectrum Antibiotic Therapy !  Antibiotics should be early and effective

!  Ideally within the first hour of diagnosis of sepsis ! Or as soon as culture samples are obtained

!  Choice depends on: ! Patient’s history (i.e., drug intolerances) ! Patient’s signalment (i.e., puppy vs. adult) ! Underlying disease (e.g., kidney dysfunction) ! Source of sepsis ! Susceptibility patterns in the hospital ! Receipt of recent antibiotics (within previous 3 months)

Broad-Spectrum Antibiotic Therapy !  Usually target gram positive and gram negative

bacteria (+/- anaerobes or others) !  Adjust antibiotics based on culture & sensitivity data

!  Ideally de-escalate to one drug within 3-5 days

!  Typical first-line therapies: ! Ampicillin/Unasyn + Amikacin ! Ampicillin/Unasyn + Enrofloxacin ! Cefazolin + Cefotaxime ! Cefoxitin ! Clindamycin + Enrofloxacin

!  Treatment for 1-2 weeks is sufficient in most cases

Drug Dose Antimicrobial Spectrum

Amikacin 15-30 mg/kg IV q 24 h Gram pos: + Gram neg: ++

Ampicillin Unasyn

20-30 mg/kg IV q 8 h Gram pos: + Gram neg: + Anaerobes: +

Cefazolin 20-30 mg/kg IV q 8 h Gram pos: + Gram neg: ± Anaerobes: ±

Cefoxitin 20-30 mg/kg IV q 6-8 h Gram pos: + Gram neg: + Anaerobes: +

Clindamycin 11-22 mg/kg IV q 12 h Gram pos: + Gram neg: + Anaerobes: +

Enrofloxacin 10-20 mg/kg IV q 24 h Gram pos: ± Gram neg: ++

Metronidazole 10-15 mg/kg IV q 12 h Anaerobes: ++

!  Retrospective study – University Teaching Hospital !  86 dogs with confirmed septic peritonitis !  Appropriate antibiotic therapy not associated with

outcome !  Prior therapy with antibiotics (within 30 days) or

recent abdominal surgery were associated with inappropriate antibiotic selection

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Source Control !  Rapid diagnosis of the specific site of infection

!  Identification of a focus of infection amenable to source control measures ! Drainage of an abscess ! Debridement of infected necrotic tissue ! Removal of potentially infected device (e.g., catheter) ! Definitive control of a source of ongoing microbial

contamination

!  Intervention within the first 12 hours of diagnosis

Underlying Etiology Suggesting Need for Surgical Procedure

!  Abdominal Exploratory: ! Gastrointestinal perforation ! Cholangitis or ruptured infected gall bladder ! Pyometra ! Parenchymal organ abscess ! Penetrating traumatic wounds

!  Joint Lavage: ! Septic arthritis

!  Debridement/Drainage: ! Abscess ! Necrotizing soft tissue infection ! Pyothorax

Diagnostic Indications for an Exploratory Laparotomy

!  Radiographs: ! Loss of serosal detail with underlying etiology ! Pneumoperitoneum (no recent surgery or

abdominocentesis) !  Ultrasound:

! Peritoneal effusion ! Underlying etiology for sepsis

!  Cytology: ! Degenerative neutrophils with foreign debris !  Intracellular bacteria

!  Fluid analysis: ! Abnormal fluid-blood measurements with underlying

etiology

Surgical Goals 1.  Identification and removal of the source of

infection 2.  Lavage to remove debris, bacteria, toxic by-

products !  > 200 mL/kg warm isotonic fluid for septic peritonitis !  Be sure to remove residual lavage fluid

3.  Consideration for post-operative drainage !  Open drainage !  Passive drainage !  Active drainage

4.  Consideration for post-operative nutrition !  Placement of a feeding tube

Open Post-operative Peritoneal Drainage

Advantages Disadvantages !  Improved drainage !  Alteration of the

anaerobic environment of the peritoneum

!  Fluid loss !  Hypoproteinemia !  Evisceration !  Continued sepsis !  Nosocomial infection !  Increased cost !  Need for repeat

sedation/anesthesia for bandage changes

!  Retrospective study !  36 dogs !  No difference in survival between open drainage vs.

primary closure !  Dogs managed with open drainage had:

! More plasma and blood transfusions ! Longer duration of hospitalization in ICU (6 days vs. 3.5

days)

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Closed Post-operative Peritoneal Drainage

Advantages Disadvantages !  Removal of bacteria,

toxins, foreign debris, residual abdominal effusion

!  Allow quantification of abdominal effusion

!  Allow easy fluid sampling for analysis

!  Drain occlusion !  Ascending

nosocomial infection !  Accidental premature

removal !  Hypoproteinemia

Hemodynamic Support of Severe Sepsis or Septic Shock

!  Adjunctive Fluid Therapy (Grade 1B) ! Crystalloids are the initial fluid of choice ! Hydroxyethyl starches no longer recommended for people ! Use fluid challenges to gauge response to therapy ! Consider albumin or plasma if hypoproteinemia

!  Vasopressors (Grade 1C) !  Instituted when fluid resuscitation does not correct

hypoperfusion ! Target MAP > 65 mmHg

!  Inotropes (Grade 1C) !  If ongoing evidence of hypoperfusion despite vasopressor

use or if documented myocardial dysfunction

Adjunctive Fluid Therapy !  Consider if:

! Crystalloid resuscitation alone is unsuccessful ! Patient is hypoproteinemic ! Patient is edematous

!  Natural colloids: ! Fresh frozen plasma or frozen plasma ! Canine lyophilized albumin

!  Synthetic colloids: ! Hydroxyethyl starches

Plasma Products (FP or FFP) !  Pre-transfusion screening

!  20 mL/kg of plasma will raise the TP by 1.0 mg/dL (10 g/L) or the albumin by 0.5 mg/dL (5 g/L)

!  Typically administered at 5-10 mL/kg/hr

!  Each unit is typically given over 4 hours

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Lyophilized Canine Albumin !  Produced by Animal Blood Resources (USA)

! 5 g vial ($150 USD per vial cost from ABR) ! Rehydrated with 30 mL of 0.9% saline, PLA, or D5W ! 16% solution once rehydrated ! Recommended dose = 2.5-5 mL/kg (maximum 2 g/kg/day) ! Maximum administration rate = 1 mL/min ! Use within 24 h of reconstitution ! Osmolality will cause ~ 120 mL of volume to shift

intravascular ! Sporadically available due to concerns of

allergic reactions

!  Prospective randomized clinical trial !  14 client-owned dogs with hypoalbuminemia post-

surgery for septic peritonitis !  800 mg/kg of canine lyophilized albumin administered

within 24 hours of surgery !  Albumin, COP, and diastolic BP increased 2 hours

later but there was no difference after 24 hours !  1 dog experienced tachypnea during transfusion and

died of unknown respiratory causes 120 hours later

Hydroxyethyl Starches !  Can be administered as bolus therapy

! 5-10 mL/kg IV over 15 minutes ! Maximum recommended dose is 20-50 mL/kg/day

!  No longer recommended for use in human septic shock patients ! Off the market in Europe ! Black box warning in USA

!  Documented coagulopathies and suspicion for acute kidney injury in dogs

Synthetic Colloids (HES)

Pros ! Provision of oncotic

support in patients with hypoproteinemia

! Longer lasting intravascular volume expansion

! Ability to expand the IV compartment using a smaller fluid volume

Cons !  Cost!

! Vetstarch® = $81 per 500 mL bag

! Pentaspan® = $58 per 250 mL bag

!  Possible side effects ! Kidney injury ! Coagulopathy

!  No proven benefit

Vasopressors !  All patients requiring vasopressors should have an

arterial catheter placed as soon as possible

!  Norepinephrine is the first choice !  Vasopressin can be added to raise MAP or decrease

norepinephrine dose !  Dopamine only recommended in patients with:

! Low risk of tachyarrhythmias ! Absolute or refractory bradycardia

!  Epinephrine can be considered as an adjunct or alternative vasopressor

!  Experimental model of septic peritonitis in Beagles !  Comparison of vasopressor doses:

! Epinephrine 0, 0.8, and 2 mcg/kg/min ! Norepinephrine 0, 0.2, and 1 mcg/kg/min ! Vasopressin 0, 1, and 4 mU/kg/min ! Dose reduced by 50% if MAP > 120 mmHg

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! Epinephrine had a harmful effect on survival that was significantly related to drug dose ! Greater decreases in pH, HCO3, BE ! Greater increases in creatinine, Phos, BUN

! Vasopressin had no effect on HR, MAP, or CI

! Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacterial doses

Inotropes ! Consider adding dobutamine 5-20 mcg/kg/min IV

CRI if: ! Echocardiographic evidence of myocardial

dysfunction ! Persistent hypotension despite norepinephrine

therapy ! Continued evidence of hypoperfusion despite

normal MAP and norepinephrine therapy

Adjunctive Therapy !  Analgesia !  Glucose control !  Nutrition !  Stress-ulcer

prophylaxis !  Blood products !  Anticoagulant therapy !  Steroids !  Nursing care

Analgesia !  Mu-agonist opioids are recommended:

! Hydromorphone 0.05 – 0.1 mg/kg IV q 4-6 hours ! Fentanyl 2 – 5 mcg/kg/hour IV CRI

!  Adjunctive analgesics can be considered: ! Ketamine 0.1 – 1.0 mg/kg/hour IV CRI ! Lidocaine 25-50 mcg/kg/min IV CRI

!  Non-steroidal anti-inflammatories should be avoided due to risk of kidney injury

Glucose Control ! Supplement dextrose during hypoglycemia

(BG < 70 mg/dL [< 4.0 mmol/L]) ! Bolus 50% dextrose 0.5 – 1 mL/kg diluted 1:4

in 0.9% NaCl or other isotonic crystalloid and give over 5 min

! Repeat BG measurement in 15 minutes ! Consider supplementation in IV fluids (2.5 –

5% dextrose) if continued hypoglycemia

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Nutrition and Anti-Nausea Therapy !  Enteral nutrition is recommended as soon as the

patient is hemodynamically stable !  Oral or enteral tube feeding !  Ideally start at 1/3 RER per day (BW x 30 + 70) !  Increase as tolerated

!  Consider anti-nausea medications to prevent vomiting and increase voluntary eating:

!  Cerenia 1 mg/kg SQ q 24 h !  Metoclopramide 0.3 mg/kg IV loading dose then

1-2 mg/kg/day IV CRI !  Ondansetron 0.2-0.5 mg/kg IV q 6-8 hours

!  Retrospective study !  45 dogs surviving from septic peritonitis !  Early nutritional support = consistent calorie intake

initiated within 24 hours after surgery ! Associated with a significantly shorter hospitalization

(by 1.6 days)

Blood Products !  Packed red blood cells:

! Consider only when PCV < 21% (target PCV 21-27%)

!  Fresh frozen plasma: ! Do not use to correct laboratory measured clotting

abnormalities in the absence of bleeding or planned invasive procedures

!  Platelets: ! Consider prophylactic transfusion if < 20,000/µL (<

20x109/L) if significant risk of bleeding ! Consider transfusion if < 50,000/µL (< 50x109/L) if

planned invasive procedure or active bleeding

Other Medications !  Stress ulcer prophylaxis

! Consider in patients with GI hemorrhage or hypotension ! Famotidine 0.5 – 1 mg/kg IV q 12 h ! Pantoprazole 1 mg/kg IV q 12-24 h

!  Anticoagulant therapy ! Consider heparin in all patients with severe sepsis ! Unfractionated heparin: ! Measure baseline aPTT ! 25-50 IU/kg IV loading dose ! 10-35 IU/kg/hour IV CRI ! Re-measure aPTT q 12 h with aim to prolong 1.5-2X

baseline

Steroids !  Consider in patients with vasopressor-dependent

septic shock for the management of critical illness related corticosteroid insufficiency (CIRCI) ! Prednisone/Prednisolone: 0.25-1 mg/kg IV every 24

hours (divided into 2 equal doses [q 12 h]) ! Dexamethasone: 0.04-0.4 mg/kg IV every 24 hours

Nursing Care & Monitoring

Nursing Care Monitoring !  Change positioning

(rotate recumbency) !  Passive range of motion !  Head above bed 30o,

sternal, or semi-sternal positioning

!  Nebulization & coupage if pneumonia

!  Wound/incision management

!  Vital signs !  Blood pressure !  ECG !  Pulse oximetry !  Lab work

! PCV, TP, BG, Lactate, Electrolytes q 6-12 h

!  Pain score

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Sabrina: Pre-op Management !  Fluid resuscitation: PLA 60 mL/kg IV over 45 min !  Then PLA 10 mL/kg/hour IV !  Hydromorphone 0.05 mg/kg IV !  Ampicillin 22 mg/kg IV !  Enrofloxacin 10 mg/kg IV !  Cerenia 1 mg/kg SQ !  Famotidine 0.5 mg/kg IV

Sabrina: Anesthesia & Surgical Management !  Pre-med:

! Hydromorphone 0.05 mg/kg IV ! Diazepam 0.5 mg/kg IV

!  Induction: Propofol to effect !  Maintenance: Isoflurane

!  Surgery (4 hours after admission) findings: ! Dehiscence and leakage from the previous enterotomy

site ! Resection and anastamosis performed + copious lavage

!  Hypotension developed during surgery ! Treated with dobutamine and norepinephrine

Sabrina: Post-op Management !  Continued pre-op treatments !  Continued norepinephrine 0.2 mcg/kg/min IV CRI

to maintain BP !  Placement of NG feeding tube !  Added unfractionated heparin:

! Baseline aPTT slightly above normal ! 50 IU/kg IV loading dose ! 20 IU/kg/hour IV CRI

!  Added metoclopramide: ! 0.3 mg/kg IV loading dose ! 1 mg/kg/day IV CRI

Sabrina: Post-op Monitoring !  PCV, TS, BG, lactate

q 8 h !  VBG, lytes, BUN

q 12 h !  TPR + SpO2 q 4 h !  Continuous ECG

and BP monitoring !  UOP monitoring !  Record GRV q 4 h

(while recumbent)

Sabrina: Outcome !  Hypotension worsened 6 hours post-op

!  Norepinephrine increased to 1 mcg/kg/min IV CRI !  Prednisone sodium succinate 0.5 mg/kg IV once

!  Hypoproteinemia developed 6 hours post-op !  PCV/TP = 32%/4.0 g/dL (40 g/L) !  Voluven 5 mL/kg IV bolus repeated twice !  Transfused 20 mL/kg frozen plasma (4 units)

!  Hypotension persisted 12 hours post-op !  Stuporous mentation !  Owner consented to humane euthanasia

!  Culture results later revealed resistant Enterococcus

!  Multicenter retrospective case series !  114 dogs undergoing surgery for septic peritonitis !  Dysfunction of each organ system included:

!  Renal (creatinine increase ≥ 0.5 mg/dL [44 µmol/L] post-op) !  Cardiovascular (hypotension requiring vasopressor therapy) !  Respiratory (need for oxygen supplementation or mechanical

ventilation) !  Hepatic (bilirubin > 0.5 mg/dL [8.6 µmol/L]) !  Coagulation (25% prolongation of PT/PTT or platelet count ≤

100,000/µL [100x109/L])

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!  Dysfunction of the following organ systems increased the risk of non-survival independently of other factors: ! Renal (OR=2.2, P=0.03) ! Cardiovascular (OR=3.4, P=0.004) ! Respiratory (OR=3.3, P<0.001) ! Coagulation (OR=4.3, P=0.02)

!  Overall mortality = 47% ! Dogs without MODS = 25% ! Dogs with MODS = 70%

!  Prospective observational study !  30 dogs with pyometra undergoing surgery !  Goal-directed protocol therapy for resuscitation pre-

and post-operatively !  Measurement of lactate, ScvO2, and base deficit to

guide management !  Analyses of these parameters to predict outcome

!  Results: ! 37% mortality rate ! All non-survivors required vasopressors ! 90% of non-survivors were in septic shock

!  Retrospective study !  83 dogs with septic peritonitis (64% survival rate) !  Admission lactate > 4 mmol/L was 36% sensitive

and 92% specific for non-survival !  Inability to normalize lactate within 6 hours of

admission was 76% sensitive and 100% specific for non-survival

!  Post-op lactate > 2 mmol/L was 46% sensitive and 88% specific for non-survival

Conclusions ! Sepsis can be a very serious condition with a

guarded to poor prognosis ! Prompt recognition and treatment with fluid

resuscitation and antibiotics are crucial ! Surgical intervention or other source control are

recommended within 12 hours ! Post-operative care and monitoring are intensive

(and expensive) ! The development of septic shock and

requirement for vasopressors are poor prognostic indicators

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Dr. Justine Lee !  NAVC 2015 !  WVC 2015

Dr. Garret Pachtinger !  NAVC 2015 !  WVC 2015

Questions? criticalcarevet@outlook.com

www.criticalcarevet.ca

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