Surgical Critical Care

Philip Goodney, MD

October 26th, 2005

Format

• Question and Answer (multiple choice)

• Review of reading in Sabiston and Greenfield Chapter

Neurologic dysfunction

• Which criteria is NOT necessary to declare brain death? – A: absence of cerebral function

– B: absence of pupillary light reflex

– C: absence of corneal reflex

– D: absence of vestibulo-ocular reflex

– E: absence of radio-isotope uptake on brain scan

– F: absence of oropharyngeal reflex

– G: apnea in the presence of “adequate stimulation” (PaCO2

> 60 mm Hg for 30 seconds).

Neurologic dysfunction

• Which criteria is NOT necessary to declare brain death? – A: absence of cerebral function – B: absence of pupillary light reflex – C: absence of corneal reflex – D: absence of vestibulo-ocular reflex – E: absence of radio-isotope uptake on brain scan– F: absence of oropharyngeal reflex – G: apnea in the presence of “adequate stimulation” (PaCO2

> 60 mm Hg for 30 seconds). – Provides supportive evidence only.

Neurologic dysfunction

– Damage to the midbrain affects level of consciousness via the

a) the reticular activating system

b) Cerebral cortex

c) Uncus

d) Internal capsule

Neurologic dysfunction

– Damage to the midbrain affects level of consciousness via the

a) the reticular activating system

b) Cerebral cortex

c) Uncus

d) Internal capsule

Neurologic dysfunction

– Depolarizing neuromuscular blockers mimic

a) Vecuronium

b) Cisatricurium

c) Acetylcholine

d) Pseudocholineserase

Neurologic dysfunction

– Depolarizing neuromuscular blockers mimic

a) Vecuronium

b) Cisatricurium

c) Acetylcholine

d) Pseudocholineserase

Succinylcholine, the only available depolarizing NMB, works by binding the acetylcholine receptors and causing depolarization (clinically seen as muscle fasciculations). Succinylcholine is characterized by a rapid onset and short half-life; it is most useful for short invasive procedures

Neurologic dysfunction

• A dose of vecuronium lasts for ___ minutes, and is cleared by the _____.

a) 15 / liver

b) 90 / kidneys

c) 10 / plasma ester hydrolysis

d) 30 / liver and kidneys

Neurologic dysfunction

• A dose of vecuronium lasts for ___ minutes, and is cleared by the _____.

a) 15 / liver

b) 90 / kidneys

c) 10 / plasma ester hydrolysis

d) 30 / liver and kidneysVec – 30 minutes, longer in px with hepatic/renal dysfunc

Panc: 90 min, don’t use in px with cardiac dx b/c vagolytic

Atricur/cistatricur: eliminated by plasma ester hydrolysis, so useful in patients with liver/kidney dysfunction

Cardiovascular dysfunction

• Patients who require afterload reduction with nitroprusside warrant observation for cyanide toxicity, as cyanide is a breakdown product of nitroprusside. How is it detected?

Cardiovascular dysfunction

• Patients who require afterload reduction with nitroprusside warrant observation for cyanide toxicity, as cyanide is a breakdown product of nitroprusside. How is it detected?– Elevated mixed venous oxygen saturation

Cardiovascular dysfunction

• Treatment of cyanide toxicity is:

Cardiovascular dysfunction

• Treatment of cyanide toxicity is:– Sodium nitrite (10 ml)– Followed by 1mg/kg methelyne blue– HD

Cardiovascular dysfunction

• Acts primarily on the heart, increasing heart rate, contractility, and atrioventricular conduction– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Cardiovascular dysfunction

• Acts primarily on the heart, increasing heart rate, contractility, and atrioventricular conduction– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Cardiovascular dysfunction

• Decreases heart rate– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Cardiovascular dysfunction

• Decreases heart rate– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Cardiovascular dysfunction

• Causes arterial vasodilation– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Cardiovascular dysfunction

• Causes arterial vasodilation– Alpha 1 – Beta 1– Beta 2– Dopamine1– Dopamine2

Pulmonary dysfunction

• At which part of the hemoglobin – O2 dissociation curve do continued increases in PaO2 result in very little increase in SaO2 ?

Pulmonary dysfunction

• At which part of the hemoglobin – O2 dissociation curve do continued increases in PaO2 result in very little increase in SaO2 ?

– Upper part of the curve

Pulmonary dysfunction

The pathogenesis of ARDS involves three stages.1. First (exudative) phase2. Second (fibroproliferative) phase3. Third (resolution) phaseWhat kind of cells are destroyed in Stg 1?a) macrophagesb) type II pneumocytesc) alveolar epitheliumd) mesenchymal cells

Pulmonary dysfunction

The pathogenesis of ARDS involves three stages.

1. First (exudative) phase

2. Second (fibroproliferative) phase

3. Third (resolution) phase

What kind of cells are destroyed in Stg 1?

a) macrophages (cause the damage)

b) type II pneumocytes

c) alveolar epithelium (disrupted, not destroyed)

d) mesenchymal cells (fill the space and initiate fibrosis)

Pulmonary dysfunction

• Low tidal volume ventilation translates into how many ml/kg tidal volumes?– 3– 6– 9– 12

Pulmonary dysfunction

• Low tidal volume ventilation translates into how many ml/kg tidal volumes?– 3

– 6

– 9

– 12

NEJM: In 861 patients, trial stopped because in-hospital mortality was 31% with Tv = 6 ml/kg, and 40% in TV 12 ml/kg

GI dysfunction

• Grade 2 abdominal compartment syndrome should be treated with:– IVF– Observation– Paralytics– Decompression

GI dysfunction

• Grade 2 abdominal compartment syndrome should be treated with:– IVF– Observation– Paralytics– Decompression

GI dysfunction

Grade IAP Rx

I 10-14 IVF

II 15-24 Supranormal IVF

III 25-35 Decompression

IV >35 Emergent decompression

GI dysfunction

• The average nutritional requirement for a patient is calculated by the Harris-Benedict equation. However, a reasonable estimate for patients of normal body habitus is ___ kcal/kg/day– 15– 30– 45– 60

GI dysfunction

• The average nutritional requirement for a patient is calculated by the Harris-Benedict equation. However, a reasonable estimate for patients of normal body habitus is ___ kcal/kg/day– 15

– 30

– 45

– 60• 35 kcal/kg/day for underweight px, 25 kcal/kg/day for overwieght

patients

GI dysfunction

• Patients with severe stress should receive ___ g/kg/day of protein in their TPN– 0.5– 1.5– 2.5– 3.5

GI dysfunction

• Patients with severe stress should receive ___ g/kg/day of protein in their TPN– 0.5– 1.5– 2.5– 3.5

– Normal – 2.0g/kg/day of protein in tpn

GI dysfunction

• Arginine.

• Glutamine

• The ω-3 fatty acids

• Nucleotides

•oxidative fuel for enterocytes and other rapidly replicating cells.

•promotes normal T-cell distribution and function and aids in wound healing.

•enhance the replication of rapidly dividing cells as well as immune responsiveness.

•compete with arachidonic acid in cyclooxygenase metabolism, resulting in production of prostaglandins of the three series and leukotrienes of the five series.

Match the nutrient with the beneficial effect

GI dysfunction

• Arginine.

• Glutamine

• The ω-3 fatty acids

• Nucleotides

•oxidative fuel for enterocytes and other rapidly replicating cells.

•promotes normal T-cell distribution and function and aids in wound healing.

•enhance the replication of rapidly dividing cells as well as immune responsiveness.

•compete with arachidonic acid in cyclooxygenase metabolism, resulting in production of prostaglandins of the three series and leukotrienes of the five series.

Match the nutrient with the beneficial effect

Renal dysfunction

• True or false: – Continuous renal replacement therapy has been

proven to be safer in the ICU patient than intermittent HD

Renal dysfunction

• True or false: – Continuous renal replacement therapy has been

proven to be safer in the ICU patient than intermittent HD

– False: While Continuous RRT techniques offer the advantage of improved hemodynamic stability and relatively less resource utilization, but they require some anticoagulation and have not been proven superior to hemodialysis in improving outcomes.

Hepatic dysfunction

• Which of these clinical entities does not exist in hepatorenal syndrome:– Decreased activity of the renin-angiotensin-

aldosterone system– Systemic vasodilation– Azotemia– High urine sodium– High urine osmolality

Hepatic dysfunction

• Which of these clinical entities does not exist in hepatorenal syndrome:– Decreased activity of the renin-angiotensin-

aldosterone system (should be increased)– Systemic vasodilation– Azotemia– High urine sodium (Una should be <10)– High urine osmolality

Hematologic dysfunction

• Heparin induced thrombocytopenia typically occurs how long after a patient is exposed to heparin?– 2 days– 4 days– 6 days– 8 days

Hematologic dysfunction

• Heparin induced thrombocytopenia typically occurs how long after a patient is exposed to heparin?– 2 days– 4 days– 6 days– 8 days (5 days if the patient has been sensitized

before)

Sepsis

• APC is an endogenous protein that

(Choose all that apply)a) Promotes fibrinolysis

b) inhibits thrombosis

c) Inhibits inflammation

d) Modulates of the coagulation cascade

e) Limits cell apoptosis

Sepsis

• APC is an endogenous protein that

(Choose all that apply)a) Promotes fibrinolysis

b) inhibits thrombosis

c) Inhibits inflammation

d) Modulates of the coagulation cascade

e) Limits cell apoptosis

Sepsis

Complications of therapy with APC, in a large RCT of 1690 patients with sepsis, was limited to

a) infection

b) seizures

c) somnolence

d) bleeding

Sepsis

Complications of therapy with APC, in a large RCT of 1690 patients with sepsis, was limited to

a) infection

b) seizures

c) somnolence

d) bleeding

Coagulopathy

Recombinant factor VIIa …

a) is contraindicated in trauma

b) induces a thrombin burst with formation of fibrin clots

c) Has no effect on measured prothrombin time

d) Activates the intrinsic coagulation cascade

e) Combines with platelets to enhance platelet plug formation

Coagulopathy

Recombinant factor VIIa …

a) is contraindicated in trauma

b) induces a thrombin burst with formation of fibrin clots

c) Has no effect on measured prothrombin time

d) Activates the intrinsic coagulation cascade

e) Combines with platelets to enhance platelet plug formation

Inflammation

All of the following cytokines or proteins are pro-inflammatory and procoagulant except:

a) tumor necrosis factora, b) interleukin-1bc) interleukin-6d) Thrombine) Activated Protein C

Inflammation

All of the following cytokines or proteins are pro-inflammatory and procoagulant except:

a) tumor necrosis factora, b) interleukin-1bc) interleukin-6d) Thrombine) Activated Protein C

PROWESS Study

• Activated protein C, endogenous protein promotes fibrinolysis inhibits thrombosis inhibits inflammation is an important modulator of the

coagulation and inflammation associated with severe sepsis

• Reduced levels correlated with increased risk of death in patients with severe sepsis

PROWESS Study

PROWESS Study

• We therefore evaluated whether the administration of drotrecogin alfa activated would reduce the rate of death from all causes at 28 days in patients with severe sepsis and have an acceptable safety profile.

PROWESS Study: Eligibility

• Known or suspected infection on the basis of

• Three or more signs of systemic inflammation • sepsis-induced dysfunction of at least one

organ or system that lasted no longer than 24 hours.

• Patients had to begin treatment within 24 hours after they met the inclusion criteria.

PROWESS Study: Treatment

• Randomized to saline or DrAA

• Dose = 24ug per kg infused over 96 hours

• Evaluation:– D-dimer (marker of coagulopathy)– IL-6 (marker of inflammation)– Mortality

PROWESS Study: Results

• Trial stopped at second interim analysis (1520 patients analyzed)

• 1728 patients randomized, 1690 received DrAA or placebo• Twenty-eight days after the start of the

infusion, 259 of 840 patients in the placebo group (30.8

percent) and 210 of 850 (24.7 percent) of the patients in the drotrecogin alfa activated group had died.

Absolute reduction = 6.1 % (p<0.005)Relative risk reduction = 19.5%

PROWESS Study: Results (Survival)

PROWESS Study: Results (IL-6)

PROWESS Study: Complications

PROWESS Study:

• Discussion points:– Was the effect of DrAA dependant upon the type

or location of the infection?– What kind of patients underwent bleeding

complications?

ADDRESS Study

• Similar study, required as part of the FDA approval of DrAA

• PROWESS: high risk patients

• ADDRESS: examine the response in patients of lower risk

ADDRESS Study

• Methods: excluded patients with high risk.

• After 1500 patients enrolled, trial was stopped because of <5% chance of effect

ADDRESS Study (results)

ADDRESS Study

• No survival effect

• Complications:– Bleeding, both during the infusion period and

subsequently thereafter in the 28 day study period.

ADDRESS Study

ADDRESS Study

• Study halted given the lack of effect, and the increased complication

• Discussion: “inexperienced sites”, “APACHE… good for populations, less useful in predicting the outcome of individual patients”

• Conclusion: No role for DrAA in low risk patients.