HIGH RISK SURGERY

Oleh:
dr. Andy

Pembimbing:
dr. Eddy Harijanto, SpAn-KIC
 PHYSIOLOGICAL RESPONSE TO MAJOR
SURGERY

- Surgical site release cytokines which mediates inflammatory cascade

- Afferent neuron release of endogenous catecholamines from the
adrenal glands and other endocrine hormones via signals in the HPA.

Catabolic phase: increased oxygen consumption (may raise to raising to

~5 ml/kg/min), metabolic changes (hyperglycaemia, increased
coagulability and redistribution of fluid between compartments)
persists for several days after operation: the magnitude of the response
varies depending on the surgery

- Oxygen demand (due to delivery failure or decreased arterial oxygen

content) not reached at risk of oxygen debt. Occult hypovolaemia
(due to fluid shifts, losses, and haemorrhage) may impair global
oxygen delivery.
- Compensatory splanchnic vasoconstriction to maintain sufficient
blood flow to vital organs GI tract vulnerable to ischaemia

Gary M, Biccard, B. Assessment of the high risk perioperative patient. Continuing Education in Anaesthesia, Critical Care & Pain. 2014;1:12-7.
 Prolonged
procedures with
large fluid
shifts/blood

Gary M, Biccard, B. Assessment of the high risk perioperative patient. Continuing Education in Anaesthesia, Critical Care & Pain. 2014;1:12-7.
SURGERY SPECIFIC SCORING SYSTEMS

General surgery: Cardiac surgery:

POSSUM (Physiological EuroSCORE European
and Operative Severity System for Cardiac
Score for the Operative Risk
enUmeration of Evaluation)
Mortality and Morbidity) STS (Society of Thoracic
P-POSSUM Surgeons mortality risk
SORT (Surgical Outcome score)
Risk Tool) Vascular POSSUM
ACS NSQIP (American
College of Surgeons
National Surgical Quality
Improvement Program)
APACHE II (Acute
Physiology and Chronic Chereshneva M, Watson X, Hamilton M, Singh H. Perioperative risk
Health Evaluation) prediction scores. Anesthesia tutorial of the week. Tutorial 343: 13
December 2016
postoperative
P
O
S
S
U
M
P
O
S
S
U
M
 POSSUM

Predicted Morbidity:

Predicted Mortality:

P-POSSUM:
 PATIENT SPECIFIC SCORING SYSTEMS

General: ASA

Cardiac risk assessments: RCRI

Pulmonary risk assessment: only for ARDS and pneumonia
Renal risk assessment: General Surgery Acute Kidney Injury
Risk Index Classification System
Liver risk assessment: Child-Turcotte-Pugh (CTP), MELD

Chereshneva M, Watson X, Hamilton M, Singh H. Perioperative risk prediction scores. Anesthesia tutorial of the week. Tutorial 343: 13 December
2016
Chereshneva M, Watson X, Hamilton M, Singh H. Perioperative risk prediction scores. Anesthesia tutorial of the week. Tutorial 343: 13 December
Chereshneva M, Watson X, Hamilton M, Singh H. Perioperative risk prediction scores. Anesthesia tutorial of the week. Tutorial 343: 13 December
2016
Chereshneva M, Watson X, Hamilton M, Singh H. Perioperative risk prediction scores. Anesthesia tutorial of the week. Tutorial 343: 13 December
2016
KASKADE KOAGULASI

Oleh:
dr. Andy

Pembimbing:
dr. Eddy Harijanto, SpAn-KIC
 PEMBEKUAN DARAH (BLOOD
COAGULATION)

Bekuan mulai terbentuk dalam 15

sampai 20 detik bila trauma pembuluh
sangat hebat, dan dalam 1 sampai 2
menit bila traumanya kecil.
Proses pembekuan darah dipengaruhi
oleh
A. Zat-zat aktivator yang berasal dari pembuluh
darah yang rusak
B. trombosit
C. Protein darah yang kontak dengan pembuluh
darah
 Mekanisme umum Blood Coagulation
1) Sebagai respon dari rusaknya pembuluh darah, terjadi
cascade reaksi kimia dalam darah yang melibatkan
faktor-faktor pembekuan darah protrombin activator
2) Protrombin activator mengkatalisir konversi protrombin
trombin
3) Trombin bertindak sebagai enzym yang mengkatalisir
fibrinogen fibrin
 Sekali satu faktor pembekuan darah aktif, maka dia
akan mengaktifkan faktor-faktor pembekuan darah yang
lain.
Rangkaian reaksi hingga terbentuknya thrombin untuk
mengkatalisis konversi fibrinogen fibrin disebut
CLOTTING CASCADE
 KONVERSI PROTROMBIN - TROMBIN

I. Protrombin aktivator dibentuk sebagai akibat

rusaknya pembuluh darah
II. Kehadiran Ca 2+ memudahkan protrombin
aktivator mengkonversi protrombin trombin
III. Trombin menyebabkan polimerisasi dari
molekul fibrinogen menjadi serabut fibrin
dalam 10 -15 detik
Trombosit juga turut berperan pada konversi
protrombin trombin
Sebelum protrombin berkonversi menjadi
trombin, ia melekat kepada protrombin
reseptor yang ada pada trombosit yang
melekat pada jaringan yang rusak
 Protrombin disintesa di hati secara terus menerus
Untuk pembentukan protrombin dibutuhkan vit K
Jumlah normal = 15 mg/dl
Kelainan pada hati dan kekurangan vit K akan
menyebabkan sintesa protrombin terganggu
 KONVERSI FIBRINOGEN-
FIBRIN
Fibrinogen disintesa di hati
Fibrinogen dapat menembus permeabilitas
kapiler darah ke cairan interstitial.
Dalam keadaan normal bisa ditemukan
fibrinogen di cairan interstitial dalam jumlah
sedikit
Fibrinogen dalam jumlah sedikit dalam cairan
interstitial tidak akan menyebabkan koagulasi
Bila terjadi peningkatan permeabilitas kapiler
darah, akan semakin banyak fibrinogen
berpindah ke cairan interstitial sehingga bisa
terjadi proses koagulasi di cairan tersebut
 Konversi fibrinogen menjadi fibrin monomer
dikalisir oleh trombin
Fibrin-fibrin monomer akan saling berikatan
untuk membentuk serat fibrin yang panjang
yang akan menjadi dasar dari blood clot
Trombin menyebabkan polimerisasi dari
molekul fibrinogen menjadi serat fibrin dalam
10 -15 detik
Fibrin polimer yang terbentuk masih dalam
bentuk ikatan yang lemah dan mudah
rusak(loose fibrin) karena fibrin monomer
berikatan dgn ikatan hidrogen non kovalen
dan serat fibrin nya tidak berkatan silang
Loose fibrin akan diperkuat oleh Fibrin
Stabilizing Factor (faktor XIII) yang terdapat di
globulin plasma
 Fibrin stabilizing factor ini akan membentuk ikatan kovalen
antara fibrin monomer dan ikatan silang antara serat fibrin
sehingga menjadi kokoh
 CLOT RETRACTION

Beberapa menit setelah blood clot terbentuk,clot

akan mulai berkontraksi dan mengeluarkan cairan
yang terdapat didalamnya cairan ini disebut serum
Trombosit mengaktifkan thrombostenin, actin-myosin
sehingga trombosit berkontraksi lebih kuat menekan
fibrin meshwork sehingga menjadi lebih kecil dan
lebih padat
Kontraksi ini dipercepat oleh trombin dan ion Ca 2+
yang dilepaskan oleh mitochondria, reticulum
endoplasma dan badan golgi fibrin meshwork yang
memadat dan mengecil ini akan menyebabkan
terjadinya CLOT RETRACTION
Begitu clot retraksi terjadi ujung-ujung pembuluh
darah yang rusak akan tertarik saling mendekat
 DISSOLUTION

Sekali bekuan darah terbentuk, maka akan

terjadi
Bekuan darah akan dipenuhi oleh fibroblasts,
yang akan membentuk jaringan ikat di sepanjang
bekuan tersebut
Penghancuran bekuan darah (lysis of clot)
Menjadi larut (dissolve)
Penghancuran bekuan darah (lysis of clot)
dikatalisir oleh plasmin (enzym proteolitic),
berasal dari plasminogen (protein plasma) yang
diaktifkan
 Plasmin mencerna benang-benang dan protein-
protein koagulan
Pada saat terbentuknya clot, plasminogen
terperangkap bersama plasma protein yang lain,
tetapi plasmin belum terbentuk
Setelah beberapa hari kemudian, jaringan yang
rusak dan endothel pembuluh darah secara
perlahan-lahan melepaskan tissue plasminogen
activator (t-PA) yang membantu konversi
plasminogen plasmin
Clot yang dipecah adalah clot yang tidak
dibutuhkan
EXTRINSIC
PATHWAY
INTRINSIC
PATHWAY
COMMON PATHWAY
COMMON
PATHWAY
 Ada beberapa faktor penting yang
mencegah terjadinya clotting pada
pembuluh darah yang normal

Faktor Endotel
1. Kehalusan dari permukaan sel endotel
yang mencegah kontak pengaktifan dari
sistem clotting
2. Lapisan glycocalix pada endotel yang
menolak/mengusir faktor faktor
pembekuan sehingga mencegah tejadinya
clotting
3. Suatu ikatan protein dengan membran
endotel, trombomodulin dengan
trombin ikatan ini tidak hanya
memperlambat proses pembekuan
dengan cara memindahkan trombin,
tapi ikatan ini juga mengaktifkan
plasma protein yaitu protein C yang
bertindak sebagai antikoagulan
dengan cara menginaktifkan faktor V
dan VII
Aksi anti trombin oleh fibrin dan
antitrombin III:
1. Setelah serat fibrin dibentuk dalam
proses clotting maka saat itu juga
trombin yang dibentuk oleh protrombin
akan diserap oleh serat fibrin tersebut
sehingga mencegah penyebaran trombin
ke dalam darah
2. Antitrombin III akan menghentikan
trombin yang tidak diserap oleh serat
fibrin dalam aksinya mengkonversikan
fibrinogen menjadi fibrin
Heparin
- Merupakan antikoagulan yang kuat yang
terdapat dalam darah
- Diproduksi oleh berbagai jenis sel dalam
tubuh tetapi yang paling banyak
menghasilkannya adalah mast cell
basophilic yang berada di connective
tissue perikapiler
- Heparin terus diproduksi oleh sel ini dan
kemudian di difusikan ke dalam sistem
sirkulasi
HIPERFIBRINOLISIS

Oleh:
dr.Andy

Pembimbing:
dr. Eddy Harijanto, SpAn-KIC
 Fibrinolysis is responsible for fibrin breakdown.
Hyperfibrinolysis occurs when fibrinolytic activity is
potentially greater than fibrin formation such that clot
integrity is threatened.
The central event of fibrinolysis is the generation of plasmin
which cleaves fibrin and fibrinogen with the release of fibrin
and fibrinogen degradation products.
 The consequences of hyperfibrinolysis af fect other aspects of
haemostasis.
Plasmin may reduce platelet adhesion and aggregation by
degradation of receptor glycoprotein lb and platelet fibrinogen
receptor glycoprotein IIb/IIIa.
The consumption of clotting factors due to the direct ef fect of
plasmin and the formation of fibrinogen degradation which
inhibit fibrin polymerisation result in poor fibrin generation.
 HYPERFIBRINOLYSIS:
PRIMARY VS. SECONDARY

Primary Secondary
Rapid clot breakdown Secondary to systemic
Increase in circulating hypercoagulability
tPA binding to fibrin Systemic or microvascular
Excess tPA Not localized
- Decreased hepatic clearance Commonly associated
-Decreased fibrinolytic with DIC
inhibitors
2-antiplasmin
PAI-1
 HYPERFIBRINOLYSIS:
PRIMARY VS. SECONDARY

Primary Secondary
Bleeding Bleeding
Rapid breakdown of clot Degradation of fibrin
Consumption of
Diminished clot formation
coagulation factors
Formation of FDPs Formation of FDPs
Inhibition of platelet Inhibition of platelet
function function
Interference with fibrin Interference with fibrin
cross-linking cross-linking
 HYPERFIBRINOLYSIS:
PRIMARY VS. SECONDARY

Primary Secondary
Treat consequence of Treat hypercoagulability
excess circulating tPA Common treatment:
Common treatment: Anticoagulant
Antifibrinolytic agent Heparin
LMWH
Warfarin
Restore endogenous
anticoagulation pathways
ATIII
APC
 Measurement of fibrinolytic activity is dif ficult in the face of
low fibrinogen concentrations.
Increased levels of fibrin degradation product titres (usually
D-dimers which are the degradation products from cross-
linked fibrin) are used routinely as a quick marker of
increased fibrinolytic activity.
However, they are crude and in situations such as
postoperative bleeding are not useful, for concentrations are
increased postoperatively in all patients.
In such situations it would be helpful to know the levels of
plasminogen activators, but these assays are time consuming
and expensive.
 If clinical bleeding can be attributed to hyperfibrinolysis, then
the use of an antifibrinolyic agent is appropriate.
Aprotinin is a powerful antiplasmin agent that, when given
continuously perioperatively, reduces bleeding during cardiac
surgery and is also used extensively during orthotopic liver
transplantation.
In established bleeding it can be given at a dose of 500 000
KIU intravenously in an emergency.
Tranexamic acid and epsilon aminocaproic acid (EACA) also
have antiplasmin properties but are less ef ficacious than
aprotinin.
 DIC CHARACTERISTICS

Disseminated Intravascular Coagulation (DIC)

Bacterial infections/sepsis
Systemic infections
Liver transplants
Vascular disorders
Severe trauma
Solid tumors and hematological malignancies
Obstetrical complications
Placental abruptions
Amniotic fluid emboli
Presence of toxins (snake venom, amphetamines, and other drugs)
 DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
Ongoing systemic activation
of coagulation Secondary
Pro-
Fibrinolysis
thrombotic

Intravascular deposition Depletion of factors

of fibrin and platelets

Thrombosis of small
and midsize vessels Bleeding

Tissue ischemia
and organ failure Levi, M & TenCate, H. NEJM. 1999;341:1999
 DIC:
DIAGNOSTIC CHARACTERISTICS
Progressive disease
No single laboratory test
Diagnosis
Clinical presentation
Bleeding and/or disease state
Laboratory tests:
Presence of soluble fibrin monomer complexes
Platelet count < 100,000/dL or rapidly decreasing platelet count
Increased PT, aPTT
Presence of FDPs
Low levels of coagulation inhibitors (ATIII)
TEG analysis to demonstrate progression of DIC
ATELECTASIS
 ATELECTASIS: CAUSES

Inhalational / intravenous anesthesia

NMBA
Neuraxial reduce insp capacity ~20%, exp reserve volume
~0
Ketamine used alone does not produce atelectasis
Positioning
Obese
Surgery cardiopulmonary bypass
Hi FiO2
 ATELECTASIS: PATHOPHYSIOLOGY

Compression of lung tissue

Trasmural pressure reduced collapsed alveoli
Diaphragm displaced cephalad, pleural pressure increased
Absorption of alveolar air
Complete airway occlusion pocket of trapped -gas continue to
be absorbed colapse of gas pocket
Low V/Q area low PaO2, when ventilated with hi FiO2
absorption >>, exceed gas flow Collapse
Hi FiO2, duration of exposure, low mixed venous oxygen, low V/Q ratio
Impairment of surfactant function
Surfactant function depressed by anesthesia
 ATELECTASIS: TREATMENT

PEEP? Reopened units collapse rapidly

after discontinuation of PEEP
Inflation of airway pressure of 40 cmH2O
for 7-8s (recruitment / vital capacity
manoeuvre) remains inflated for at
least 40 mins
 STRESS
HYPERGLYCEMIA
 ILLNESS LEADS TO STRESS
HYPERGLYCEMIA
Illness
Stress Hormones
cortisol, epinephrine Glucose Production
+

FFAs
Glucose
Fatty Acids
Lipolysis

Glucose Uptake

FFAs
STRESS HYPERGLYCEMIA EXACERBATES
ILLNESS
Illness
Stress Hormones
cortisol, epinephrine Glucose Production
Hemodynamic + insult
Electrolyte losses
Oxidative stress
FFAs
Glucose Myocardial injury
Hypercoagulability
Fatty Acids Altered immunity
Lipolysis
Wound healing
Glucose Uptake Inflammation
Endothelial function
FFAs
 GUIDELINES FROM PROFESSIONAL ORGANIZATIONS
ON THE MANAGEMENT OF GLUCOSE LEVELS IN THE
ICU

Updated
Target Since
Treatment Glucose Definition of NICE_SUGAR
Year Organization Patient Population Threshold Level Hypoglycemia Trial, 2009
2009 American Association of ICU patients 180 140-180 <70 Yes
Clinical Endocrinologists and
American Diabetes
Association
2009 Surviving Sepsis Campaign ICU patients 180 150 Not stated Yes

2009 Institute for Healthcare ICU patients 180 <180 <40 Yes
Improvement
2008 American Heart Association ICU patients with 180 90-140 Not stated No
acute coronary
syndromes
2007 European Society of ICU patients with Not stated Strict Not stated No
Cardiology and European cardiac disorders
Association for the Study of
Diabetes

Kavanagh BP, McCowen KC. N Engl J Med. 2010;363:2540-2546.

 AACE/ADA RECOMMENDATIONS:
ALL PATIENTS IN CRITICAL CARE
Blood glucose target: 140-180 mg/dL
Intravenous insulin infusion prefered
Hypoglycemia
Reassess the regimen if blood glucose level is <100 mg/dL
Modify the regimen if blood glucose level is <70 mg/dL

Moghissi ES, et al. Endocr Pract. 2009;15:353-369.

 INDICATIONS FOR IV INSULIN THERAPY

Diabetic ketoacidosis NPO status in type 1

Nonketotic diabetes
hyperosmolar state Labor and delivery
Critical care illness Glucose exacerbated by
(surgical, medical) high-dose
Postcardiac surgery glucocorticoid therapy
Myocardial infarction or Perioperative period
cardiogenic shock After organ transplant
Total parenteral
nutrition therapy

ACE Task Force on Inpatient Diabetes and Metabolic Control. Endocr Pract. 2004;10:77-82.
 COMPONENTS OF IV INSULIN THERAPY

Concentrations should be standardized throughout the

hospital
Regular insulin in concentrations of 1 U/mL or 0.5 U/mL
Infusion controller adjustable in 0.1-U doses
Accurate bedside blood glucose monitoring done hourly (every
2 hours if stable)
Potassium should be monitored and given
if necessary

Clement S, et al. Diabetes Care. 2004;27:553-591.

 ACHIEVING GLYCEMIC TARGETS
IN THE ICU

a. Van den Berghe G, et al. N Engl J Med. 2001;345:1359-1367. b. Goldberg PA, et al. Diabetes Care. 2004;27:461-467.
c. Davidson PC, et al. Diabetes Care. 2005;28:2418-2423; d. Finfer S, et al. N Engl J Med. 2009;360:1283-1297.
 EXAMPLE: UPDATED YALE INSULIN
INFUSION PROTOCOL
Insulin infusion: Mix 1 U regular human insulin per 1 mL 0.9%
NaCl Administer via infusion pump in
increments of 0.5 U/h

Blood glucose target range:

120-160 mg/dL
Use glucose meter to monitor blood glucose hourly

Bolus and initial infusion rate:

Divide initial BG by 100, round to nearest 0.5 U
for bolus and initial infusion rates
Example: Initial BG = 325 mg/dL: 325/100 = 3.25, round up to 3.5:
IV bolus = 3.5 U + start infusion at 3.5 U/h

Subsequent rate adjustments:

Changes in infusion rate are determined by the current infusion
rate and the hourly rate of change from the prior BG level
Shetty S, et al. Endocr Pract. 2012;18:363-370.
 AN OPTIMAL IV INSULIN PROTOCOL

Validated
Reaches and maintains blood glucose successfully within a
prespecified target range
Includes a clear algorithm for making temporary corrective
changes in the IV insulin rate, as patient requirements change
Incorporates rate of change in BG, not just the absolute
values
Incorporates the current IV insulin rate
Minimizes hypoglycemiaprovides specific directions for its
treatment when it occurs
Provides specific guidelines for timing and selection of doses
for the transition to subcutaneous insulin

69
 BEDSIDE GLUCOSE MONITORING

Point-of-care measurement
Most practical and actionable for guiding treatment
But need to consider limitations in accuracy
Strong quality-control program essential
Specific situations rendering capillary
tests inaccurate
Shock, hypoxia, dehydration
Extremes in hematocrit
Elevated bilirubin, triglycerides
Drugs (acetaminophen, dopamine, salicylates)

Clement S, et al. Diabetes Care. 2004;27:553-591.

Kanji S, et al. Crit Care Med. 2005;33:2778-85.
 IV INSULIN PROTOCOLS
KEY POINTS
Several published protocols for intravenous insulin infusions
Each may be suitable for different patient populations
Ideal protocol: one that will work in a given institution
All protocol implementation will require multidisciplinary interaction
and education
Other protocols needed to make inpatient glucose
management a success include
Protocols to manage hypoglycemia
Protocols to guide the transition from intravenous to subcutaneous
therapy