Title: Management of Acute Variceal Bleeding in A EAAU Dr Mark McCullen, Royal Bournemouth Hospital
1Management of Acute Variceal Bleeding in
AE/AAUDr Mark McCullen, Royal Bournemouth
Hospital
2Natural History and Prognosis
- In patients with cirrhosis cumulative incidence
varices ? from 12 to 90 over 12 years - Those with varices have 20-60 chance of bleeding
during f/u - 70 of bleeding episodes occur within 1st 2
years of follow up
3Natural history and prognosis
- Alcoholic cirrhotics will develop varices at a
rate of 8 per year - In gt 50, varices will enlarge
- Incidence of variceal bleeding in patients who
have never bled 4.4 - Mortality of first bleed 25 - 50 (depending on
Child-Pugh class) - 50 - 70 incidence of late rebleeding
4Risk Factors for Variceal Haemorrhage
- Bleeding occurs at rupture sites related to
- Portal pressure (Hepatic Venous Pressure Gradient
HVPG ? 12mmHg) - Intravariceal Pressure
- Variceal Size
- Liver Failure
- Infection (endotoxin)
- Not related to erosions, ulcers or oesophagitis
5Acute variceal bleeding
- Factors associated with early mortality
- severity of liver disease
- active bleeding
- failure to control bleeding
- infection (common in cirrhosis)
- renal dysfunction
- concomitant cardiorespiratory disease
6Acute variceal bleeding
- Goals of therapy
- restore blood volume
- stop bleeding rapidly
- prevent early rebleeding
- prevent and treat complications
- prevent deterioration of liver function
7Presentation and diagnosis
- Hypotension, haematemesis, malaena
- History
- risk factors for chronic liver disease
- previous variceal bleeds
- medication- ? ß- blockers, hypotensives
- recent NSAIDS
- abdominal surgery
- pancreatitis/umbilical vein sepsis
8Presentation and diagnosis
- Examination
- stigmata of chronic liver disease
- encephalopathy
- cardiovascular compromise (postural BP)
- signs of aspiration
- hepato/splenomegaly/ascites
- hepatic bruits
9Investigations
- FBC
- Clotting screen
- UEs
- LFTs
- Glucose
- CXR
- MSU
- Blood cultures
- Ascitic tap
10Acute variceal bleeding
- Initial approach
- resuscitation - restore blood volume
- therapy - vasoactive drugs immediately
- - antibiotics
- diagnosis - endoscopy
- - endoscopic therapy
11- Resuscitation (and factors that may compromise
outcome) - A Airway - aspiration
- B Breathing - encephalopathy
- - endoscopy
- - tense ascites
- C Circulation - blood loss -
vasodilation - cirrhosis - - secondary to sepsis
- - sedatives (eg midazolam/propofol)
- Transfer to high nursing dependency-bed
12Acute variceal bleeding
- Transfusion
- avoid over-transfusion (animal model data)
- - Hct 30 / Hb 10 g/l
- - RA pressure nearly equal to 5 mmHg
- (intravariceal pressure correlates with
CVP - Staritz, 1992)
- replace clotting factors / platelets (no data)
- - platelet transfusion if lt 50 x 109/l
platelets - - FFP every 4 units / blood
- precautions for massive transfusion
-
13Drugs in acute variceal bleeding
- Can be given in casualty (bolus vs infusion)
- Door - needle time
- May stop bleeding
- May buy time
- Support other organs
-
- Vasopressin
- Terlipressin (Glypressin)
- Somatostatin
- Octreotide
14Vasopressin
- Infusion
- 45 incidence of side-effects
- 25 serious, requiring cessation of therapy
- Control of bleeding in 50 of 417 episodes of
variceal haemorrhage in 15 randomised controlled
trials
15Glypressin (Terlipressin/Triglycyl Lysine
vasopressin)
POR for failure to control bleeding 0.31
(0.15-0.61)
- Synthetic analogue of vasopressin
- Intrinsic vasoconstrictor activity
- Bolus
- Complication rate significantly lower than
vasopressin (GTN) in five unblinded trials - Does not increase concentration of plasminogen
activator
16The Levacher graph
Survival actuarial curves for TER-GTN and DP
groups. Survival analysis at day 15 and day 42
shows a significant difference between the two
groups (day 15, p0.015 day 42, p0.034).
17Somatostatin and Octreotide
- Somatostatin
- 14 amino acid peptide
- bolus and infusion
- low incidence of side-effects
- - abdominal pain feature of bolus
- Octreotide
- octapeptide sharing four amino acids with
somatostatin, but with longer half-life - variable pharmacological efficacy, with
significant tolerance - correct dose?
18Randomised placebo controlled trials of
Somatostatin/Octreotide
19- Infection prevention, treatment
- ascitic tap, blood cultures, CXR, MSU on
admission - prophylactic antibiotics (Bernard et al., 1999, -
meta-analysis) - - oral quinolones well absorbed
- treatment on suspicion of sepsis - intravenous
antibiotics - cirrhotics more at risk of sepsis (Rajkovic and
Williams, 1985) - bleeding enhances risk of sepsis- SBP 50
(Stephan et al., 1987) - haemorrhagic shock enhances bacterial
translocation (Deitsch et al., 1988)
20Prophylactic Antibiotics in GI bleeding in
cirrhotics (Bernard et al., 1999)
Survival - mean improvement 9 (p 0.0042)
Active treatment
61
Placebo
56
55
52
47
42
35
29
26
26
68
72
60
59
46
45
30
34
60
60
Rimola 1985
Soriano 1992
Blaise 1994
Pauwels 1996
Hseih 1998
The studies used a range of drugs, ranging from
gut steralisation (Rimola - Gent, Nystatin,
Vancomycin) to oral antibiotics (Sofiano,
Norfloxacin 800mg/d for 7 days) to a combination
(Pauwels, oral ciprofloxacin plus amoxycillin and
clavulanic acid IV).
21Summary of Management in AE/AAU
- Resuscitate
- Low threshold for intubation (encephalopathic/aspi
ration) - Prophylactic antibiotics
- - 3rd generation Cephalosporins IV
- - Oral Quinalones
- Treat proven sepsis aggressively
- Terlipressin/Glypressin
- 2mg IV bolus then 1 2mg every 4 - 6
hrs - up to a maximum of 48 hrs
- If delay in endoscopy /- on-going bleeding
consider - 1) Octreotide
- 2) Sengstaken Blakemore Tube
22Endoscopic Therapy Banding
23Endoscopic Therapy Banding
24Endoscopic Therapy Sclerotherapy
25Uncontrolled variceal bleeding
26Sengstaken Blakemore tube
27Balloon Tamponade
- 4-lumen Minnesota/Sengstaken-Blakemore tube
- Controls bleeding in 90 of patients
- 15 complication rate
- Use limited to 24 hours
- Oesophageal balloon only inflated if gastric
balloon does not control bleeding
28Uncontrolled variceal bleeding
OESOPHAGEAL Continued bleeding despite two
sclerotherapy/banding sessions and vasoactive
therapy during a 7-day period or Bleeding past a
Sengstaken-Blakemore tube independent of number
of sclerotherapy sessions GASTRIC Continued
bleeding despite endoscopic/vasoconstrictor
therapy
29 TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT
30- Portosystemic encephalopathy
- treat precipitant factors
- Lactulose (via fine bore NG tube- SAFE),
Phosphate enemas - Alcohol withdrawal
- obtain history (recent intake, previous fitting,
collateral history-family/friends) - IV Chlormethiazole requires constant nursing/risk
of oversedation/cannot be reversed - high dose oral or IV Thiamine in all alcoholic
patients
31Acute variceal bleeding
- Nutrition
- exacerbation of malnutrition common
- inadequate and unappealing hospital diet (most
contain maximum of 1500 cal/day) - anorexia
- nil by mouth
- 24 h after bleeding has stopped - fine bore
nasogastric feeding tube, low sodium feed - thiamine and folate in alcoholics (IV)
- alleviate tense ascites - paracentesis
32- Ascites and renal function
- at risk of acute tubular necrosis and hepatorenal
failure - maintain adequate intravascular volume (avoid
crystalloids) - urinary catheter - accurate fluid balance
- avoid nephrotoxic drugs
- Dopamine (renal dose)
- vasoconstrictive agents- Terlipressin
- paracentesis for tense ascites
- early enteral feeding (low sodium)
- early therapeutic antibiotics
- The efficacy of these drugs has not yet been
fully proved.
33Acute oesophageal variceal bleeding
34Diagnosis of Variceal bleeding
- Criteria for definitive diagnosis
- active bleeding (spurting or oozing at
oesophageo-gastric-junction) - white nipple sign (Adherent clot)
- Criteria for likely diagnosis
- varices without other lesions
- white nipple sign (Siringo et al., 1991) / cherry
red spots - If no diagnosis initially, repeat endoscopy
mandatory, which will establish a diagnosis in
over 75 of cases, particularly when associated
with rebleeding - Not all varices are upper GI
35Ectopic (stomal) varices
36Acute variceal bleeding
- Portosystemic encephalopathy
- Alcohol withdrawal
37Variceal Sclerotherapy
38OESOPHAGEAL VARICESENDOSCOPIC SCLEROTHERAPY
- Injection sclerotherapy first reported in 1939
- 1940 - 1955 multiple reports but enthusiasm was
greater for shunt surgery - 1960 - Wodak reports paravariceal sclerotherapy
- 1972 - Johnston and Rodgers report 93 success
rate in acute bleeding (194 episodes using
adaptedrigid oesophagoscope) - 1977 - Williams and Dawson reported 58 1 year
survival in 52 patients but 4 deaths from
perforation - 1980 - development of flexible overtube
39ENDOSCOPIC SCLEROTHERAPY - TECHNIQUE
- Inject at or within 2-3 cm of OGJ- rupture of
varices is almost always at this level - Intravariceal or paravariceal sclerotherapy
produce similar results(for paravariceal
injection use smaller volumes, 0.5ml risk of
ulceration and necrosis) - Use flexible endoscope, consider overtube or
balloon to control bleeding during procedure - Sclerosant Ethanolamine oleate or sodium
tetradecyl sulphate
40Sclerotherapy techniques
- Leave 12 oclock varix until last
- Lift head of bed if gastric fundus obscured by
clot - Hypotensive effect of propofol (cf. ketamine)
- Beware midazolam in alcoholics
41OESOPHAGEAL VARICESENDOSCOPIC SCLEROTHERAPY -
COMPLICATIONS
- Non-fatal 10-30Fatal 1-7
- Early Bleeding, perforation, aspiration,
mediastinitis, mural thrombosis, sepsis - Late Ulceration, full thickness necrosis and
mediastinitis, strictures - Risk of ulceration is not related to frequency of
sclerotherapy - N-Acetyl cysteine
42ENDOSCOPIC SCLEROTHERAPY - CLINICAL TRIALS
- Acute variceal bleeding controlled by
sclerotherapy in 90 of bleeds (vs 30 mortality) - Prophylactic sclerotherapy - earlier bleeding and
increased mortality in some studies - May be appropriate if signs of recent haemorrhage
- (ß-Blockers effective as primary and secondary
prophylaxis - decrease portal pressure)
43OESOPHAGEAL VARICESENDOSCOPIC SCLEROTHERAPY -
CLINICAL TRIALS
- REPEATED COURSES - REBLEEDING RATES
- Sclerotherapy
ControlKCH (1985) 55
82Cape Town (1983) 58
77Los Angeles (1984) 50
80 - statistically significant
44OESOPHAGEAL VARICESENDOSCOPIC SCLEROTHERAPY -
CLINICAL TRIALS
- Survival advantage in all studies up to 6 weeks
- Overall 50-60 mortality at 1 year in all studies
in both treated and control groups - Patients mostly died of liver failure not GI
bleeding if they survived the initial bleed
45OESOPHAGEAL VARICESENDOSCOPIC LIGATION (BANDING)
- Ensnaring of mucosa and submucosa containing
varices causing strangulation, sloughing and
fibrosis - First reported in 1992 (Stiegmann et al) fewer
complications, better survival rates - Meta-analysis indicatesDecreased rebleeding
(0.52 OR) and mortality (0.67)Decreased
complications strictures and ulcer bleedingNo
effect on chest infections and sepsisFewer
treatment sessions required to obliterate varices
46Endoscopic banding
47ENDOSCOPIC VARICEAL LIGATION
- UK study (Gimson et al, 1993) faster
obliteration, decreased rebleeding, no effect on
complications - ? Outcome with sclerotherapy depends on operator
expertise
48ENDOSCOPIC VARICEAL LIGATIONTECHNIQUES
- Stiegmann-Goff endoscopic ligator - needs
overtube - Speedband (Microvasive) 5 bands preloaded
- Saeed six shooter (Wilson-Cooke)
- Vari-loop variceal ligator (endoloops)
49ENDOSCOPIC VARICEAL LIGATION vs SCLEROTHERAPY
- ADVANTAGES More effective, fewer complications,
technically easier, decreased mortality,decreased
rebleeding, shorter treatment course - DISADVANTAGES More expensive, takes longer,
less useful for acute bleeding,difficult to use
for small varices
50Surgery for Variceal Bleeding
- Portosystemic Shunts
- Very effective but
- High mortality
- High risk of encephalopathy
- Useful in non-cirrhotic portal hypertension
- Oesophageal Transection
- Effective but very high mortality
51Uncontrolled variceal bleeding
52Uncontrolled variceal haemorrhage
Failed sclerotherapy
53Transjugular intrahepatic portosystemic shunt
Varices
Catheter into portal vein
54Transjugular intrahepatic portosystemic shunt
Balloon inflation of intrahepatic tract
Intrahepatic tract
Sengstaken balloon
55Transjugular intrahepatic portosystemic shunt
Post transjugular intrahepatic portosystemic
shunt deployment with rapid flow up stent
56Transjugular intrahepatic portosystemic shunt
Variceal embolisation via transjugular
intrahepatic portosystemic shunt
TIPS
57Transjugular intrahepatic portosystemic shunt
- Richter et al 1990
- Artificial creation of portosystemic shunt
- Effective for uncontrolled bleeding
- Effective in hypertensive gastropathy,
colopathy, - gastric/ectopic/stomal varices
- Superior to shunt surgery
- Reduced risk of rebleeding compared to
sclerotherapy - Greater risk of encephalopathy
- Good bridging measure to transplantation