Anaesthesia
Research Review
Making Education Easy
Issue 14 – 2012
Welcome to issue 14 of Anaesthesia Research Review.
In this issue:
This edition of Anaesthesia Research Review includes a variety of papers, and in some instances suggests further reading
for those who are interested. Topics range from the increased use of preoperative echocardiography to routine use of IV
equipment. Three areas of particular interest are the consequences of discovery of whole bodies of research that are ‘faulted’;
the review of data (some of which were never collected with the aims of the study in mind) to test the authors’ current
hypothesis and the impact of a new drug or technique on publications. One of the more recent episodes of faulted data
involves the research into antiemetics by Professor Fujii – the sheer volume of his publications over many years has distorted
the findings of more than one meta-analysis investigating the relative efficacies of antiemetics in the treatment of PONV.
The appearance of a novel way of terminating the effects of nondepolarising muscle relaxants (sugammadex) has seemingly
been accompanied by an interest in NMB, which includes ‘data mining’ to highlight the possible deficiencies of practice to
date. Each of these topics may, indirectly, say as much about the nature of research and medical publishing as they do about
the science underlying anaesthesia.
Intermediate-acting NMBs and
postop respiratory complication
risk
Errors during preparation of
drug infusions
Distractions/interruptions in
anaesthetic practice
Cartoons reduce anxiety in
children during anaesthesia
induction
Thank you for your comments and feedback – please keep them coming.
Kind regards,
Regional vs. general anaesthesia
for hip fracture surgery
Naloxone and posthysterectomy
morphine consumption
Impact of TTE in hip fracture
surgery patients at risk of
cardiac disease
Dr Malcolm Futter
malcolmfutter@researchreview.co.nz
Intermediate acting non-depolarizing neuromuscular
blocking agents and risk of postoperative respiratory
complications
Authors: Grosse-Sundrup M et al
Summary: These researchers prospectively investigated the association between intermediate-acting NMB agents and
postoperative respiratory complications in a cohort of 18,579 surgical patients who received such agents and an equal
number of propensity score-matched reference patients who did not. NMB agent use was associated with significantly
increased risks of postoperative, postextubation oxygen desaturation <90% (main outcome measure) and reintubation
requiring unplanned ICU admission (respective ORs 1.36 [95% CI 1.23, 1.51] and 1.40 [1.09, 1.80]), and these risks were
increased by neostigmine reversal (1.32 [1.20, 1.46] and 1.76 [1.38, 2.26]). Furthermore, the risks were not attenuated by
qualitative monitoring of neuromuscular transmission.
Two premed intranasal
dexmedetomidine doses in
children
Systemic metoclopramide to
prevent PONV
Comment: Anaesthetists reading the introduction to this paper will immediately recognise it has been written for a
nonspecialist journal, particularly when reference is made to Beecher and Todd’s 1954 paper! The study is a review of
the Massachusetts General Hospital database over a period during which more than 220,000 surgical procedures were
undertaken, approximately one quarter of which were accompanied by general anaesthesia, intubation and ventilation.
Surprisingly, about 40% of this group received either no relaxant or only suxamethonium, which probably does not reflect
NZ practice. Although controls were in many respects ‘matched’ to patients receiving intermediate-acting relaxants, with
regard to the surgery performed, there was apparently only the ability to select by specialty. Thus, all other things being
equal, a patient having a ‘minor’ general surgical procedure could be matched against someone having a laparotomy.
Setting aside questions about the study population and the ‘matching’ process, the results are interesting because they
‘reinforce’ the recently increased scrutiny of ‘traditional’ use of nondepolarising relaxants, including monitoring of NMB
and neostigmine reversal (see editorial, Anesthesiology 2012;117[5]:934–6).
Preventing IV bacterial injection
from hands
Abbreviations used in this issue
IV = intravenous
NMB = neuromuscular block
NNT = number needed to treat
OR = odds ratio
PONV = postoperative nausea and vomiting
TTE = transthoracic echocardiography
.COM
Reference: BMJ 2012;345:e6329
http://www.bmj.com/content/345/bmj.e6329
Regional anaesthesia education
for anesthesiologists
Anaesthesia Research Review
Independent commentary by Dr Malcolm Futter, who is currently a Specialist
Anaesthetist working (towards retirement) in Auckland. Until recently he was Executive
Clinical Director at Capital and Coast District Health Board with responsibility for
Anaesthesia, ICU, Pain Management and Children’s Health. For full bio CLICK HERE.
Research Review publications are intended for New Zealand health professionals.
www.ULTRASOUNDBLOCK.com.
SITE EDITOR
MICHAEL J FREDRICKSON, FANZCA, MD
www.researchreview.co.nz
Anaesthesia Research Review is also made available
to Anaesthetists through the kind support of the
New Zealand Society of Anaesthetists
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Anaesthesia Research Review
Errors during the preparation of drug infusions
Authors: Adapa RM et al
Summary: Nurses with critical care experience (n=48) were randomly assigned to preparation of vasopressor infusions
by diluting concentrated drugs from ampoules or use of prefilled syringes during management of simulated patients
with septic shock. As expected, the time taken to start infusions was significantly shorter when the nurses used the
prefilled syringes compared with de novo preparation (156 vs. 276 sec; p<0.0001). Moreover, medication errors were
17.0 times less likely when prefilled syringes were used. Prefilled syringes (prepared by pharmacy and industry) were
significantly more likely to contain the expected concentrations of adrenaline (epinephrine; p=0.001) and noradrenaline
(norepinephrine; p<0.001), with one nurse-prepared ampule containing 20% of the expected adrenaline concentration
and another containing none at all.
Comment: No surprises here, the ability of humans to make mistakes during all stages of the process of drug
administration is well described, particularly when working under stress, Somewhat disappointingly, the authors make
little reference to the multitude of factors that may have contributed to the errors and focus on a single possible
solution (albeit a very effective one). The lack of discussion in this study contrasts with that in the next paper, which
examined distraction in anaesthetic practice.
Reference: Br J Anaesth 2012;109(5):729–34
http://bja.oxfordjournals.org/content/109/5/729.abstract
Distraction and interruption in anaesthetic practice
Authors: Campbell G et al
Summary: This paper reported that 424 distracting events were observed among anaesthetists during a total of
30 complete anaesthetic procedures in a variety of surgical settings. The frequencies of distracting events during
induction, transfer to theatre, maintenance and emergence were 0.29, 0.33, 0.15 and 0.5 per minute, respectively. The
observers judged 22% and 3% of the distracting events to have negative and positive impacts, respectively. They noted
the following strategies for managing distractions: i) ignoring inappropriate intrusions or conversation; ii) asking other staff
with nonurgent matters to come back at a quieter time; iii) preparing and checking equipment and drugs beforehand;
iv) acting as an example to other staff with respect to timing of their own potentially distracting actions; v) awareness of
one’s own emotional and cognitive state.
Comment: Notwithstanding practice differences (e.g. lack of induction rooms), the findings of this study will sound
familiar to most of us. One of the strengths of this paper is the discussion of the causes and consequences of
distraction with possible solutions. Some of these can be ‘low tech’ – a few years ago I noticed a DIY store had a
notice asking customers not to talk to staff whilst the latter were in the process of tinting paints, shortly thereafter a
prominent notice appeared on the operating room wall above the anaesthesia locker reminding staff not to talk to the
anaesthetist when they were preparing medicines!
Cartoon distraction alleviates
anxiety in children during
induction of anesthesia
Authors: Lee J et al
Summary: Children aged 3–7 years (ASA physical status I–II;
n=130) were randomised to one of the following three groups:
toy group (allowed to play with their own favourite toy until
anaesthesia induction); cartoon group (watched their selected
animated cartoon until anaesthesia induction); or iii) control
group. Modified Yale Preoperative Anxiety Scale (mYPAS)
and parent-recorded anxiety visual analogue scale scores
were significantly lower in the toy group than the cartoon
and control groups in the preanaesthesia holding room
(respective p values 0.007 and 0.02), while significantly lower
scores were seen in the cartoon group in the operating room
(p<0.001 for both). Transition from the preanaesthesia to the
operating room was associated with respective increases in
mYPAS and visual analogue scale scores in 3 and 5 children
from the cartoon group, compared with 25 and 32 children
in the toy group and 32 and 34 children in the control group
(p<0.001). No anxiety (mYPAS score <30) in the operating
room was seen in 43% of children from the cartoon group,
23% from the toy group and 7% from the control group.
Comment: Parents will smile reading this paper and
a preceding one in the same journal that looked at
inhalation induction of anaesthesia – both demonstrate
the power of moving images to distract and possibly
‘relax’ children! It is thus strange that it has taken so
long for studies such as these to appear. As a paediatric
anaesthetist, I was still using everything from mindless
chatter (no problem…) to magic wands to put patients
at ease and facilitate induction long after my dentist had
mounted a TV in his surgery ceiling. Putting aside the
dangers of ‘too much TV’, the therapeutic ratio for an
anxiolytic regimen based on cartoons far exceeds that of
most pharmacological ones.
Reference: Br J Anaesth 2012;109(5):707–15
Reference: Anesth Analg 2012;115(5):1168–73
http://bja.oxfordjournals.org/content/109/5/707.abstract
http://www.anesthesia-analgesia.org/content/115/5/1168.abstract
When it comes to NMB reversal
minutes count
When it comes to choosing NMB reversal
so do dollars
From the 1st of March 2012, BRIDION
will be available at a significantly
reduced price. Contact your MSD
Hospital Product Specialist Sandy Tully
(Wellington & South 021 662 305) or
Kim Percy (North 021 593 354) for more.
Predictable. Complete. Rapid.1
References: 1. BRIDION NZ Data Sheet. BRIDION® (Sugammadex) is an unfunded Prescription Medicine. Indications: Reversal of neuromuscular blockade induced by
rocuronium or vecuronium. Dosage & Administration: Immediate reversal of intense block. 16.0 mg/kg IV, three minutes following administration of rocuronium (1.2 mg/kg) in
adults, elderly, obese patients, patients with mild and moderate renal impairment and patients with hepatic impairment. Routine reversal of profound block. 4.0 mg/kg IV following
rocuronium- or vecuronium-induced block when recovery has reached 1-2 post-tetanic counts; in adults, elderly, obese patients, patients with mild and moderate renal impairment,
and patients with hepatic impairment. Routine reversal of shallow block. 2.0 mg/kg IV following rocuronium- or vecuronium-induced block when recovery has occurred up to
reappearance of T2; in adults, elderly, obese patients, patients with mild and moderate renal impairment and patients with hepatic impairment;2.0 mg/kg IV following rocuronium
in children and adolescents (2-17 years). Contraindications: Hypersensitivity to sugammadex or to any of the excipients. Precautions: Repeated exposure in patients;
respiratory function monitoring during recovery; use for reversal of neuromuscular blocking agents other than rocuronium or vecuronium; severe renal impairment; severe hepatic
impairment; use in ICU; allergic reactions; pregnancy (Category B2); lactation; infants less than 2 years of age including neonates; prolonged neuromuscular blockade (sub-optimal
doses) and delayed recovery. Interactions: Potential identified with toremifene, fusidic acid, flucloxacillin, hormonal contraception. Could interfere with progesterone assay and
some coagulation parameters. Adverse Reactions: Dysgeusia, prolonged neuromuscular blockade, anaesthetic complication (restoration of neuromuscular function), allergic
reactions, and events associated with surgical procedures under general anaesthesia. Date of preparation: July 2009. Please refer to full prescribing
information available at www.medsafe.govt.nz. ® BRIDION is a registered trademark, marketed in New Zealand by MSD, Auckland. First issued February
2012. ANES-1010741-XXXX. TAPS MW1711 INSIGHT 4577
For more information, please go to http://www.medsafe.govt.nz/
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Anaesthesia Research Review
Comparative effectiveness of
regional versus general anesthesia
for hip fracture surgery in adults
Naloxone infusion and post-hysterectomy morphine
consumption
Authors: Neuman MD et al
Summary: This study randomised 90 patients, aged 35–55 years, scheduled for total abdominal hysterectomy
to receive postoperative ultralow-dose IV naloxone 0.25 µg/kg/h (n=45) or saline (n=45) for 24 hours; all
participants received standard general anaesthesia, and patient-controlled analgesia with morphine in recovery.
Compared with saline, naloxone infusions were associated with significantly less morphine consumption during
the first 24 postoperative hours (19.5 vs. 27.5mg; p<0.001) and significantly reduced incidence and severity
of PONV. The incidence of pruritus and pain scores at rest and activity did not differ significantly between the
groups.
Summary: This retrospective study of 18,158 patients who had
undergone hip fracture surgery in US hospitals reported that compared
with general anaesthesia, regional anaesthesia recipients (29%) were
significantly less likely to die in hospital (adjusted OR 0.710 [95% CI
0.541, 0.932; p=0.014]) or experience pulmonary complications (0.752
[0.637, 0.887; p<0.0001]). Subgroup analyses revealed that regional
anaesthesia improved survival and reduced pulmonary complications in
patients with intertrochanteric fractures, but not in those with femoral
neck fractures.
Comment: Like the study reviewing respiratory morbidity following
nondepolarising relaxants, this one used an enormous database to
retrospectively find any association between the type of anaesthesia
used and patient outcomes. The investigators initially examined
the ‘completeness’ of anaesthesia coding within the database,
which resulted in >30% of patients with a diagnosis of fractured
neck of femur being excluded from the study. Thereafter, coding
of fracture type, comorbidities, treatments and outcomes were
examined. The discussion included a review of the multiplicity of
similar previous studies, and the authors were open in admitting the
limitations of using a database that was unable to provide complete
information, e.g. any reasons for the use of regional versus general
anaesthesia that may have influenced outcomes. Notwithstanding
the methodological criticisms, one cannot but feel, having read this
study and some of its predecessors, that central neural blockade is
the way to go (echocardiography findings permitting – see the paper
to the right by Canty et al)
Authors: Movafegh A et al
Comment: Despite the ‘somewhat conflicting’ findings of previous studies, the results of this one are
consistent with a model in which endogenous opioid ligands can bind to both an ‘inhibitory’ G-protein
coupled µ-receptor to cause analgesia or to an excitatory one that would cause hyperalgesia. If the affinity
of antagonists for the excitatory receptor type is such that even at very low concentrations it is blocked, then
they will effectively enhance the ‘normal’ inhibitory effect of opioid µ-receptor analgesics. The authors of
this paper provided a good review of these postulated mechanisms. It will be interesting to see if this latest
addition to our knowledge of how opioids may work results in changes to our analgesic regimens. As was
demonstrated with ‘sequential analgesia’ (high doses of a potent agonist followed by a higher affinity partial
agonist to reverse respiratory depression without loss of analgesia), the clinical success of such regimens
requires both the dynamics and kinetics of the agents to be comparable.
Reference: Acta Anaesthesiol Scand 2012;56(10):1241–9
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-6576.2012.02764.x/abstract
The impact on cardiac diagnosis and mortality of
focused transthoracic echocardiography in hip
fracture surgery patients with increased risk of
cardiac disease
Authors: Canty DJ et al
Reference: Anesthesiology 2012;117(1):72–92
Summary: These researchers retrospectively compared mortality rates after hip fracture surgery between patients
at risk of cardiac disease who had received preoperative TTE (n=64) and a random sample of historical controls
who had not received TTE (n=66). Compared with patients who had not received TTE, those who had received TTE
had lower rates of mortality at 30 days (4.7% vs. 15.2%; p=0.047) and 12 months (17.1% vs. 33.3% [p=0.031];
adjusted hazard ratio 0.41 [95% CI 0.2, 0.85; p=0.016]). No association was seen between preoperative TTE and
delay in surgery.
http://tinyurl.com/Anesth-117-72
Congratulations
Dr Dexter Bambery
from Wellington
Comment: Whilst the authors admit that further study is required because some uncontrolled factors may
have contributed to the result, this retrospective study from Melbourne makes a strong case for the use
of TTE in many patients presenting with fractured neck of femur. An accompanying editorial from the UK
(Anaesthesia 2012;67[11]:1189–93) reinforces the view that TTE should become near routine in this patient
population, and notes that the increased reimbursement available when surgery for fractured neck of femur
is undertaken quickly more than compensates for the costs of the TTE examination! Interestingly, one of the
consequences of the growing awareness of potential cardiovascular problems in this patient population is
a tendency towards greater use of general anaesthesia (see the paper reviewed previously in this issue on
type of anaesthesia and outcomes). Furthermore, there is nothing to suggest that apart from age, those who
fracture their femurs are unique in having comorbidities that can be detected with TTE…
who is the winner of the first
of two Ipads that we are
giving away as part our recent
subscriptions update competition.
The second iPad will be drawn
and announced before Christmas.
Reference: Anaesthesia 2012;67(11):1202–9
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.2012.07300.x/full
Renu Borst is the new Executive Officer for the New Zealand Society
of Anaesthetists (NZSA). She commenced her role on 29 October 2012.
Renu has experience working for both private and public entities in the health sector over the
past 10 years. Prior to this role she was the Corporate Services Manager for the Central Regions
Technical Advisory Service (TAS) which is a shared services agency jointly owned by the
six Central Region DHBs. Renu is very passionate about health, technology and providing value
to our members and stakeholders.
Renu Borst
Mobile: 021 518 229
Email: nzsa@anaesthesia.org.nz
For more information about the Society please contact the
NZSA office on 04 494 0124 or visit our website
www.anaesthesiasociety.org.nz.
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Anaesthesia Research Review
A randomised comparison of two intranasal dexmedetomidine
doses for premedication in children
Authors: Yuen VM et al
Summary: These researchers randomised children aged 1–8 years to receive intranasal dexmedetomidine 1 μg/kg or 2 μg/kg
in this study. Satisfactory sedation had been achieved at the time of anaesthetic induction in 53% and 66% of the low- and
high-dose recipients, respectively. A logistic regression analysis revealed no difference between the doses in participants
aged 1–4 years, while the higher dose was associated with a greater rate of satisfactory sedation in those aged 5–8 years
(ORs 1.1 [0.5, 2.7] and 10.5 [1.4, 80.2], respectively; p=0.049 for interaction). No adverse haemodynamic events were recorded.
Comment: The Malaysian and Hong Kong investigators studied a similar aged group of children as the Korean group
investigating cartoon distraction, although in this instance the patients enrolled were only those thought to benefit from
a sedative premedication. Both behaviour (including apparent anxiety) and sedation were scored, but these different
characteristics are simply described in the results as ‘sedation’. The results probably add little to what is already known
(intranasal dexmedetomidine sedation is effective in children and accompanied by a slight decrease in blood pressure),
but the discussion does review some of the current knowledge and practicalities of intranasal drug administration.
What is lacking is a discussion of the differences in the mechanism of action of dexmedetomidine and more traditional
sedatives – a third study group receiving intranasal midazolam would have made an interesting comparison. However, the
accompanying editorial written by NZ’s Professor Jamie Sleigh (Anaesthesia 2012;67[11]:1193–7) provides very good
‘background’ reading on the site and mechanism of action of dexmedetomidine.
Reference: Anaesthesia 2012;67(11):1210–6
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.2012.07309.x/abstract
Systemic metoclopramide to prevent postoperative nausea
and vomiting
Authors: De Oliveira Jr GS et al
Summary: This was a systematic review and meta-analysis of 30 randomised controlled trials investigating systemic
metoclopramide 10mg (n=3328) for PONV prophylaxis; trials from Fujii et al that have had their validity questioned since
being included in previous analyses were excluded. Compared with controls, metoclopramide was found to be associated
with reduced incidences of 24-hour PONV (OR 0.58 [95% CI 0.43, 0.78; NNT 7.8]), 24-hour postoperative nausea alone
(0.51 [0.38, 0.68; NNT 7.1) and 24-hour postoperative vomiting alone (0.51 [0.40, 0.66; NNT 8.3]). A post-hoc analysis
that included the three eligible Fujii et al trials that have had their validity questioned revealed no significant benefit of
metoclopramide versus controls on the incidence of 24-hour PONV.
Comment: This study represents yet another chapter in the PONV saga, in which metoclopramide, having had its efficacy
dismissed, is ‘rehabilitated’ when previous meta-analyses are discovered to have been flawed because of the inclusion of
‘faulted’ studies. Whilst those of us who continued to believe that when given in adequate dosage the drug was a useful
prokinetic may feel vindicated, the major interest in this saga concerns the impact of Fujii’s publications. Richard Waldron’s
article in the September edition of the ANZCA bulletin is good background reading, along with an editorial in a recent issue
of Anaesthesia (Anaesthesia 2012;67[10]:1063–7).
Prevention of intravenous
bacterial injection from
health care provider hands:
the importance of catheter
design and handling
Authors: Loftus RW et al
Summary: These researchers randomised 486 operating
room environments to one of the following three groups:
1) injection of the novel Ultraport zero stopcock with hub
disinfection before injection; 2) injection of the Ultraport
zero stopcock without prior hub disinfection; and 3) injection
of the conventional open-lumen stopcock closed with sterile
caps according to usual practice (control). The primary
anaesthesia provider in each operating room environment
performed a series of five injections of sterile saline
through the device assigned to that room into an ex vivo
catheter system after they had induced anaesthesia in their
patient. Effluent bacterial contamination was eliminated
in group 1 (with disinfection) compared with group 2
(without disinfection) and the control group (0% vs. 4% and
3.2%, respectively). Glove use by the provider significantly
increased the risk of effluent contamination (risk reduction
10.48 [95% CI 3.16, 34.80; p<0.001]). A controlled
laboratory experiment resulted in the estimated quantity of
bacteria injected reaching the clinically significant threshold
of 50,000 colony-forming units per each injection series.
Comment: The very ‘basic’ nature of peripheral IV
cannulation and the associated equipment often
means it receives little attention in the anaesthesia
literature. However, because of the growing awareness
of potential bacteraemia, perhaps we should pay more
attention! Aside from showing how infrequently injection
ports are disinfected before use, an interesting aside
of this study is the association between glove wearing
and contamination. Personally the latter finding came
as no surprise, having observed for years the relative
disregard of contamination by glove wearers when
compared with the more fastidious behaviour of those
whose skin is potentially contaminated.
Reference: Br J Anaesth 2012;109(5):688–97
Reference: Anesth Analg 2012;115(5):1109–19
http://bja.oxfordjournals.org/content/109/5/688.abstract
http://www.anesthesia-analgesia.org/content/115/5/1109.abstract
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