Download Vol 6 #1 - Vancouver Acute Pharmaceutical Sciences

February 1999
Volume 6, Number 1
fied
In This Issue...
Changes to Formulary
Cefamandole Interchange to Cefazolin
Alternative to Racemic Epinephrine
Antiemetic Prophylaxis for PONV
Amoxicillin-Clavulanate (Clavulin®)
Awards - CSU Pharmaceutical Sciences
Infusion Program Updates
Adverse Drug Reaction Report 1998
1
2
2
3
4
5
5
6
All formulary changes and policy/procedure updates have been
approved by the Drugs and Therapeutics Committee (D&T) and
Medical & Academic Advisory Council (MAAC).
This and other D&T Newsletters are on the Web at www.
vhpharmsci.com
Changes to Formulary
Changes to Formulary
Deletions
1. Cefamandole 1g, 2g vials (Mandol®)
• on March 15, 1999, all orders for cefamandole will be interchanged to cefazolin
(gram for gram)
• see page 2 for interchange policy
2. Cortisporin® ear drops (polymixin B/
neomycin/hydrocortisone)
• alternative: Garasone® eye/ear drops
3. Tolcapone tablets (Tasmar®)
• new antiparkinsonian agent recently suspended by manufacturer due to safety
concerns
• may still be obtained through the Special
Access Program (SAP)
Additions
Updated Policies/Procedures
1. Amoxicillin/clavulanate 500/125 mg,
875/125 mg (Clavulin®)
• Oral antibiotic possessing broad spectrum
antibacterial activity
• See page 4 for drug review
1. Revised Drug Administration Policies
2. Garasone® eye/ear drops (gentamicin
3mg/mL and betamethasone 1.0mg/mL)
• antibacterial and anti-inflammatory drops
• Cost: $12.82/7.5mL
3. Dakin’s Solution 1:8,1:16 (dilute sodium
hypochlorite)
• the 1:16 dilution will be the default
strength supplied if a strength is not speci-
•
Alteplase (t-PA) may now be administered
direct IV by nurses in ICU, CCU-1, Emergency-Acute and Cardiac Cath Lab.
EDITORIAL STAFF:
Karen Shalansky, Pharm.D.
Peter Loewen, Pharm.D.
Rubina Sunderji, Pharm.D.
Peter Jewesson, Ph.D.
Any comments, questions or concerns with the content of the newsletter
should be directed to the editors. Write to CSU Pharmaceutical Sciences
Vancouver General Hospital, 855 W12th Ave, Vancouver BC V5Z 1M9,
send a FAX to 604-875-5267 or email [email protected]
Find us on the Web at www.vhpharmsci.com
Drug and Therapeutics Newsletter
2. Cefamandole Interchange to Cefazolin
Carlo Marra, Pharm.D., Luciana Frighetto, B.Sc. (Pharm), Peter
Jewesson, Ph.D.
Effective March 15, 1999, all orders for cefamandole will be subject to a therapeutic interchange with an equivalent regimen of cefazolin
(Table 1). The previous cefamandole to cefuroxime interchange will no longer apply. Cefuroxime will still remain on formulary. Cefamandole is being deleted as it offers no advantage over other formulary antibiotics, is more
expensive than cefazolin, and its use has declined significantly. At VHHSC, cefamandole no
longer demonstrates in vitro superiority over
cefazolin with respect to Staphylococcus epidermidis. The Division of Medical Microbiology
has previously discontinued reporting susceptibility patterns for cefamandole.
Table 1. Cefamandole to Cefazolin Conversion
Cefamandole Dose
Cefazolin Dose Conversion
1 g IV q6h or q8h
1g IV q8h
2g IV q6h or q8h
2g IV q8h
In this institution, cefamandole has been used
primarily for surgical prophylaxis in cardiac, orthopedic, and vascular procedures. As part of
the Standardized Orders for Antimicrobial Prophylaxis (SOAP) initiative, a review of the antimicrobial surgery prophylaxis literature was recently conducted by members of the CSU Pharmaceutical Sciences. Guidelines were subsequently developed in collaboration with representatives from various surgical divisions for different procedures. The Divisions of Cardiac, Orthopedic, and Vascular Surgery have adopted
cefazolin as their antibiotic of choice for surgery
prophylaxis in non-beta-lactam allergic patients.
Preprinted orders are now being created for
many surgical procedures reflecting standard
protocols for both pre-operative and postoperative antimicrobial prophylaxis.
Under the therapeutic interchange policy, if
2
Volume 6, Number 1
cefamandole is prescribed, it will be interchanged
to the same dose of cefazolin at an equivalent
interval (Table 1). This policy has been approved
by the Antibiotic Utilization Subcomittee, D&T
(November 1998) and MAAC (January 1999).
3. Alternative to Racemic Epinephrine
Racemic epinephrine, used in the treatment of
reversible bronchospasm and laryngeal edema,
has been back-ordered indefinitely by the manufacturer. Racemic epinephrine contains equal
amounts of the d- and l-isomers of epinephrine,
with the l-isomer being more pharmacologically
active.
The alternative to nebulized racemic epinephrine
is nebulized l-epinephrine. L-epinephrine has
been shown to be as effective as racemic epinephrine with no additional adverse effects.1-3
The dose for l-epinephrine 1:1000 (1mg/mL) is
10-fold the volume required for racemic epinephrine. The adult dose is :
5 mL (5mg) l-epinephrine 1:1000 = 0.5mL racemic epinephrine 2.25%
Due to the volume required, l-epinephrine does
not need to be further diluted for nebulization.
The solution should be administered over 10-15
minutes. CSU Pharmaceutical Sciences will clarify all orders for racemic epinephrine with the
physician and these will be corrected to lepinephrine. L-epinephrine 1:1000 30mL injectable will be supplied.
L-epinephrine and racemic epinephrine both
contain metabisulphite and should not be used in
patients with sulphite hypersensitivity.
References
1. Kanji Z. Shortage of racemic epinephrine - is epinephrine an
alternative? BCCH Pharmacy Informer. Spring/Summer 1998.
2. Waisman Y et al. Prospective randomized double-blind study comparing l-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatr 1992;89:302-6.
3. Nutman J et al. Racemic versus l-epinephrine aerosol in the treatment of post-extubation laryngeal edema: results from a prospective,
randomized, double-blind study. Crit Care Med 1994;22:1591-4.
Drug and Therapeutics Newsletter
3
Volume 6, Number 1
postoperative nausea and vomiting. Can J Anaesth 1997;44:173-81.
4. Antiemetic Prophylaxis for Post-Operative
Nausea and Vomiting
Luciana Frighetto, B.Sc. (Pharm), Carlo Marra, Pharm.D., Peter
Loewen, Pharm.D.
Post-operative nausea and vomiting (PONV)
are commonly reported adverse events after
surgery and can contribute to the development
of aspiration, wound dehiscence, and increased
bleeding.1,2 Prophylaxis with antiemetics has
been shown to reduce the incidence of PONV
as well as improve patient satisfaction, decrease recovery and discharge times, and reduce hospital readmissions.3-10 There are many
studies supporting the use of prophylactic antiemetics to reduce the incidence of PONV in patients at high risk for PONV.3,7-9,11-18 Several different antiemetics have been studied for the
prevention of PONV including metoclopramide,
perphenazine, droperidol, ondansetron and
dolasetron.3-5,7,11,19-21 These agents have all
been associated with varying degrees of success.
Currently, there are no standard guidelines for
the prophylactic use of antiemetics in the management of PONV in our institution. CSU Pharmaceutical Sciences, in collaboration with the
Department of Anesthesia, have developed
standard protocols for the prevention and immediate post-operative treatment of patients
with nausea and vomiting for both the ambulatory and inpatient settings. For the prevention
of PONV, preprinted orders for anesthesia and
Surgical Daycare Centre (SDCC) have been
created for patients considered at high risk for
PONV and include various antiemetic agents
such as droperidol, dolasetron, and metoclopramide. Dolasetron, a Limited Access Drug at
VHHSC, has now been approved by the Drugs
and Therapeutics Committee and Medical Academic and Advisory Committee for use in the
prophylaxis of PONV. This agent can be prescribed using a preprinted anesthesia or SDCC
pre-op order form. Preprinted orders have also
been created for the treatment of PONV in the
post anaesthesia recovery and surgical daycare settings. These orders reflect a standard
approach for the treatment of PONV in these
settings.
References
Amoxicillin/Clavulanate
1. Burns K. Postoperative care (Clavulin®)
and review of complications. AmbulaCarlo Marra,
Pharm.D., Luciana
Frighetto,
B.Sc.
(Pharm)
tory Anesthesia
Care. Woo
SW (ed.).
Boston.
Little, Brown & Co.
1982:27-34.
2. Haigh CG et al. Nausea and vomiting after gynaecological surgery:
Amoxicillin/clavulanate
is a combination product conA meta-analysis of factors affecting their incidence. Br J Anaesth
taining1993;71:517-22.
amoxicillin, a semi-synthetic penicillin, and
3. $-lactamase
Malins AF et al. Nausea
and vomiting
after gynaecological
laparosthe
inhibitor,
clavulanate
potassium.
copy: comparison of premedication with oral ondansetron, metoClavulanate
enhances
the
antibacterial
spectrum of
clopramide,
and placebo. Br
J Anaesth
1994;72:231-233.
4. Graczykby
SG acting
et al. Intravenous
for the“suicide”
prevention of
amoxicillin
as an dolasetron
irreversible
innausea and vomiting after outpatient laparoscopic
hibitorpostoperative
of
intracellular
and
extracellular
$-lactamases
surgery. Anesth Analg 1997;84:325-30.
1,2
and,
thus protecting
deactivation
of amoxicillin.
5. Helmers
JH et al. A single
IV dose of ondansetron
8 mg prior to
induction
of anaesthesia
reduces postoperative
nauseamediated
and vomitWith the
continued
increase
in resistance
ing in gynaecological patients. Can J Anaesth 1993;40:1155-61.
by6.theOrkin
bacterial
of $-lactamases,
the adFK. Whatproduction
do patients want?
- preferences for immediate
recovery (abstract). Anesth
dition postoperative
of amoxicillin/clavulanate
to Analg
the 1992;74:S225.
VHHSC drug
7. Tang Jappears
et al. A comparison
of costs and
efficacy of
formulary
warranted.
Addition
ofondansetron
amoxiciland droperidol as prophylactic antiemetic therapy for elective outlin/clavulanate
was procedures.
proposed
by Analg
the 1996;83:304-13.
Antibiotic Utilipatient gynecologic
Anesth
8. Gold
BS et al. Unanticipated
hospitaland
following
zation
Subcommittee
in admission
Octoberto the
1998,
apambulatory surgery. JAMA 1989;262:3008-10.
proved
by
the
D&T
and
MAAC
in
November
1998
9. Fancourt-Smith PF et al..Hospital admissions from the surgical
and January
1999,
respectively.
daycare centre
of Vancouver
General Hospital 1977-1987. Can J
Anaesth 1990;37:699-704.
10. Fortier J et al. Unanticipated admission after ambulatory surgery Spectrum
of Activity
a prospective
study. Can J Anaesth 1998;45:612-19.
11. Paxton LD et al. Prevention of nausea and vomiting after day case
gynaecological laparoscopy: A comparison of ondansetron, droAmoxicillin/clavulanate
provides additional coverage
peridol, metoclopramide, and placebo. Anaesth 1995;50:403-6.
over
Staphylococcal
aureus,
Hemophi12. amoxicillin
Wrench IJ et al.of
The
prevention of postoperative
nausea
and vomiting using a combination
of ondansetron
and droperidol.
Anaesth
lus influenzae,
Escherichia
coli, Moraxella
catarrha1996;51:776-8.
lis,13.Klebsiella
Bacteroides
fragilis
and
Khalil SN et pneumoniae,
al. Ondansetron prevents
postoperative
nausea and
1,2
vomiting
in
women
outpatients.
Anesth
Analg
1994;79:845-51.
Proteus species. Consequently, this agent can be
14. Pearman MH. Single dose intravenous
in the prevenused
as an alternative to 2nd andondansetron
3rd generation
oral
tion of postoperative nausea and vomiting.
Anaesthesia
cephalosporins
1994;49:11-15. and/or cotrimoxazole for skin and
15. tissue
Lopez-Olaondo
L et al. including
Combination of
ondansetron
and lower
dexasoft
infections
bite
wounds,
methasone in the prophylaxis of postoperative nausea and vomitrespiratory
and urinary tract infecing. Br Jtract
Anaesthinfections,
1996;76:835-40.
16. Desilva
et al.meta-analysis
The efficacy of prophylactic
ondansetron,
tions.
In a PHDP
recent
that pooled
three
droperidol, perphenazine, and metoclopramide in the prevention of
decades
of
trial
results
from
more
than
four
hundred
nausea and vomiting after major gynecologic surgery. Anesth
publications
and 38,500 patients, amoxicillin/
Analg 1995;81:139-43.
17.
Gan
TJ
et
al.
ondansetron,
droperidol
clavulanate wasDouble-blind
equal orcomparison
superiorofto
other antibiotics
and saline in the prevention of postoperative nausea and vomiting.
for theBri treatment
of upper and lower respiratory inJ Anesth 1994;72:544-7.
fections,
skin
infections,
dental
infections,
18. Naguib
M et structure
al. Prophylactic
antiemetic therapy
with ondansetron,
and metoclopramide
in patients
undergohead tropisetron,
and neckgranisetron
infections,
and selected
urinary
tract
ing laparoscopic cholecystectomy: a randomized, double-blind
infections.
In addition,
the results
of these tricomparison
with placebo.when
Can J Anesth
1996;43:226-31.
Madej
TH, Simpson
Comparison
the use of domperidone,
als19.were
grouped
byKH.
annual
and oftriennial
publication
and metoclopramide in the prevention of nausea and
dates,droperidol,
the
efficacy
of
amoxicillin/clavulanate
did not
vomiting following major gynaecological surgery. Br J Anaesth
appear
to
have
changed
over
time
indicating
its
con1986;58:884-87.
20.
Sniadach
MS
et
al.
A
comparison
of
the
prophylactic
antiemetic
tinued usefulness.
effect of ondansetron and droperidol on patients undergoing gynecologic laparoscopy. Anesth Analg 1997;85:797-800.
21. Diemunsch P et al. Intravenous dolasetron mesilate ameliorates
Dosage
The established adult oral dosing regimen for amoxicillin/clavulanate is 500/125 mg given every eight
Drug and Therapeutics Newsletter
New Drug/Drug Products
Amoxicillin/Clavulanate (Clavulin®)
Carlo Marra, Pharm.D., Luciana Frighetto, B.Sc. (Pharm)
Amoxicillin/clavulanate is a combination product
containing amoxicillin, a semi-synthetic penicillin, and the $-lactamase inhibitor, clavulanate
potassium. Clavulanate enhances the antibacterial spectrum of amoxicillin by acting as an irreversible “suicide” inhibitor of intracellular and
extracellular $-lactamases and, thus protecting
deactivation of amoxicillin.1,2 With the continued
increase in resistance mediated by the bacterial
production of $-lactamases, the addition of
amoxicillin/clavulanate to the VHHSC drug formulary appears warranted. Addition of amoxicillin/clavulanate was proposed by the Antibiotic
Utilization Subcommittee in October 1998, and
approved by the D&T and MAAC in November
1998 and January 1999, respectively.
4
Volume 6, Number 1
trials have indicated that the administration of a
new 875/125 mg oral preparation twice daily is
as effective as the three times daily regimen for
lower respiratory tract infections4 and acute bacterial maxillary sinusitis.5 Table 2 compares the
dosage and cost of amoxicillin/clavulanate to
amoxicillin alone and other formulary alternaTable 2. Cost comparison of Clavulin® to other
oral formulary alternatives
Drug
Dose
Daily Costa
Amoxicillin/
Clavulanate
500/125mg tid
875/125mg bid
$4.00
$4.63
Amoxicillin
500mg tid
$0.27
Cefuroxime
axetil
500 mg tid
$11.88
Cefixime
400 mg daily
$4.47
Cotrimoxazole
1 DS tablet bid
$0.22
a
Spectrum of Activity
Amoxicillin/clavulanate provides additional coverage over amoxicillin of Staphylococcal
aureus, Hemophilus influenzae, Escherichia
coli, Moraxella catarrhalis, Klebsiella pneumoniae, Bacteroides fragilis and Proteus species.1,2 Consequently, this agent can be used
as an alternative to 2nd and 3rd generation oral
cephalosporins and/or cotrimoxazole for skin
and soft tissue infections including bite wounds,
lower respiratory tract infections, and urinary
tract infections. In a recent meta-analysis that
pooled three decades of trial results from more
than four hundred publications and 38,500 patients, amoxicillin/clavulanate was equal or superior to other antibiotics for the treatment of
upper and lower respiratory infections, skin
structure infections, dental infections, head and
neck infections, and selected urinary tract infections. In addition, when the results of these trials were grouped by annual and triennial publication dates, the efficacy of amoxicillin/
clavulanate did not appear to have changed
over time indicating its continued usefulness.
Dosage
The established adult oral dosing regimen for
amoxicillin/clavulanate is 500/125 mg given
every eight hours; however, some recent adult
based on VHHSC acquisition costs
tives.
Adverse Effects
The incidence and spectrum of adverse effects
with amoxicillin/clavulanate is similar to amoxicillin alone. Adverse effects are typically gastrointestinal in nature and include diarrhea, nausea,
vomiting and indigestion. The 875/125 mg bid
dosing schedule has resulted in a lower rate of
gastrointestinal complications than the
500/125mg tid dosing regimen.4,5 There have
been rare reports of hepatic dysfunction associated with the use of this agent, mainly in elderly
patients receiving prolonged or repeated treatment courses.2
References
1. Todd PA et al. Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use.
Drugs 1990;39:264-307.
2. Ball P et al. Amoxicillin clavulanate: an assessment after 15 years
of clinical application. J Chemother 1997;9:167-98.
3. Neu HC, Wilson APR, Gruneberg RN. Amoxicillin/clavulanic acid:
A review of its efficacy in over 38,500 patients from 1979 to 1992.
J Chemother 1993;5:67-93.
4. Calver AD et al. Dosing of amoxicillin/clavulanate given every 12
hours is as effective as dosing every 8 hours for treatment of lower
respiratory tract infections. Clin Infect Dis 1997;24:570-4.
5. Seggev JS et al. A combination of amoxicillin and clavulanate every
12 hours vs. every 8 hours for treatment of acute bacterial maxillary
sinusitis. Arch Otolaryngol Head Neck Surg 1998c; 124(8):921-5.
Drug and Therapeutics Newsletter
Pharmacy Awards
CSU Pharmaceutical Sciences is pleased to announce it has received the following national
Canadian Society of Hospital Pharmacists
(CSHP) Awards:
• Organon Award (Residency Project Award)
Sunderji R, Campbell L, Shalansky KF, Fung
A, Carter C, Gin K for
“Outpatient selfmanagement of warfarin therapy: a pilot
study.”
5
Volume 6, Number 1
the need arose.
Infusion Device Facts and Tips:
• Mechanical phlebitis is the most common
side effect of a newly inserted PICC. It will
appear within 72 hours and usually resolves
well with moist, continuous heat for 24
hours.
•
The primary cause of a "positional" PICC is
a twisted or kinked line between the suture
wing and the PICC hub.
•
A PICC dressing will always have a gauze
dressing under the occlusive dressing for
the first 24 hours only (for occasional bleeding); subsequent dressings will only have
the occlusive dressing.
•
A gauze dressing should not be placed under an occlusive dressing for longer that 24
hours as it traps heat and moisture and will
increase the risk of infection.
•
If you see fluid under an occlusive dressing,
check to see that the extension tubing is
firmly attached to the PICC hub.
•
When doing IV/CVC site preparation, use
firm pressure, moving from the centre outwards.
•
Following the removal of a CVC, the best
dressing to apply is a gauze and occlusive
dressing. These should be removed again
in 24 hours.
•
Four benefits of a Groshong close-ended
catheter are that no heparin flush is required, no clamp is necessary, bleeding
from the catheter is unlikely and air emboli
is extremely uncommon .
•
Huber point needles are now available in a
20 gauge, 3/4" length for leaner patients.
This size is adequate for blood withdrawal
and administration of medications.
•
A patient teaching booklet entitled "Total
Parenteral Nutrition - A guide for Patients
and Their Families" is available for distribution and can be ordered from Lori Mason at
• Hoffman LaRoche Award (Specialty Practice
Award) de Lemos J, Carr R, Shalansky KF,
Bevan D, Ronco J for “Paralysis in the critically ill: intermittent bolus pancuronium compared with continuous infusion.”
• Novartis Award (Pharmacoeconomics Award)
Frighetto L, Marra C, Loewen P, Doleman J
for “Cost effectiveness of prophylactic dolasetron or droperidol for prevention of postoperative nausea and vomiting in outpatient gynecologic surgery.”
Infusion Program Updates
Did you know that...
• The Home IV Antibiotic Program has been
operating successfully for over 36 months,
has enrolled over 265 patients who received
over 6,200 outpatient antibiotic treatment
days.
•
•
A 1997 13-month cost benefit analysis of
the Home IV Antibiotic Program revealed an
estimated net cost avoidance of over
$440,000. In other words, for every 12
cents VHHSC contributes to the program, a
cost avoidance of $1.00 is achieved.
All patients who are enrolled into the Home
IV Antibiotic Program are asked to complete
a satisfaction survey at the end of treatment.
A 1998 18-month analysis of surveys revealed that on a 10-point scale, the median
rank of patient satisfaction with the program
is 10. In fact, 95% of patients enrolled in the
program state they would participate again if
Drug and Therapeutics Newsletter
6
Volume 6, Number 1
Adverse Drug Reaction Report 1998
There were a total of 40 suspected adverse drug reactions (ADRs) reported at VHHSC in 1998
(Table 3). Of note, 12 reactions were considered to have been the cause of hospitalization. The continued reporting of all suspected ADRs by nurses, physicians and pharmacists aids in an improved assessment of the magnitude and nature of adverse events. To notify Pharmacy of an ADR, either fill
out a yellow ADR alert card, available on all nursing units, and send to CSU Pharmaceutical Sciences, or call local 62481 (VGH site) or local 27249 (UBC site). Pharmacists complete all ADR report
forms and forward copies to the B.C. Regional ADR Centre. This Centre does preliminary analysis of
the data and then forwards all reports to the Canadian ADR program in Ottawa who then forward
them to the World Health Organization.
Table 3. Adverse Drug Reactions Reported in 1998
Drug
Suspected ADR
Drug
Suspected ADR
a
Abciximab (in conjunction
with heparin & ticlopidine)
thrombocytopenia (4)
Levothyroxine
chest pain/tightness (in relation to dose increase (1)
Allopurinola
rash, lip swelling, conjunctival discharge, fever, eosinophilia (1)
Lithiuma
(interaction with hydrochlorothiazide)
tremors, ataxia, decreased
level of consciousness, required hemodialysis (1)
Amitriptyline
ventricular tachycardia (1)
Methotrimeprazine
granulocytopenia (1)
Anileridine
pruritic rash on back and
abdomen (1)
Niacin
flushing (1)
Bupropion
erythematous rash (1)
Nitrofurantoina
pulmonary fibrosis (1)
Carbamazepine
neutropenia, falling platelet
count (1)
Phenytoin
rash, fever with rigors (1)
Cefazolin
angioedema, swollen lips,
flushing (1)
Phenytoin/Carbamazepinea
hypersensitivity reaction (1)
(rash, fever, periorbital swelling, lymphadenopathy)
Ciprofloxacin
myoclonic jerks (1)
Propylthiouracil
neutropenia (1)
Cisapride
increased saliva and drooling (1)
Ranitidine
Cotrimoxazole
elevated LFTs (1)
Rifampina
a
pruritic rash, periorbital and
lip swelling (1); delirium (1)
acute interstitial nephritis (1)
a
Donepezil
excessive drooling, rhinorrhea (1)
Tamoxifen
deep vein thrombosis (1)
Droperidol
intense dysphoria, altered
mental state, nightmares x 6
weeks after dose (1)
Ticlopidinea
thrombotic thrombocytopenic purpura (1)
Enalapril/
Hydrochlorothiazidea
agranulocytosis (1)
Tolcaponea
anxiety, agitation (1)
Fludrocortisone + Valerian
hypokalemia (1)
Vancomycin
nephrotoxicity (1)
a
Glucosamine
gastritis (1)
Warfarin
Iron Dextran
rash, chest pain, chills (1);
back pain (1)
Zopiclone
Ketorolac
anaphylaxis (known allergy
to NSAIDS) (1)
a
hospitalized due to ADR
rash (1); GI bleed (1, in conjunction with ASA and ticlopidine), GI bleed (1, in conjunction wtih ASA)
black-out, fall (1)