TOP TEN SELECTED PAPERS - March 2009

1

Br J Anaesth. 2009 Mar 31. [Epub ahead of print]

Propofol concentration in exhaled air and arterial plasma in mechanically
ventilated patients undergoing cardiac surgery.

Grossherr M, Hengstenberg A, Meier T, Dibbelt L, Igl BW, Ziegler A, Schmucker P, 
Gehring H.

Department of Anaesthesiology.

BACKGROUND: /st> Measuring propofol concentration in plasma (c(P)PL) and in
exhaled alveolar gas (c(P)G) during constant infusion provides information about 
their respective time courses. In the present study, we compared these time
courses in patients undergoing cardiac surgery from the beginning of propofol
anaesthesia until eye opening upon awakening. METHODS: /st> The c(P)G was
measured before, during, and after continuous infusion of propofol for general
anaesthesia in 12 patients at two randomly allocated doses (3 or 6 mg kg(-1)
h(-1)). Gas samples were collected on Tenax tubes. After thermodesorption, c(P)G 
was measured by gas chromatography mass spectrometry. Simultaneously with exhaled
gas, arterial blood was sampled for measuring c(P)PL by reversed-phase
high-performance liquid chromatography with fluorescence detection. In order to
compare the time courses of c(P)PL and c(P)G as dimensionless values directly,
each gas and plasma value was normalized by relating it to the corresponding
value at the end of the initial infusion after 40 min. RESULTS: /st> The c(P)G
ranged between 2.8 and 22.5 ppb, whereas the corresponding c(P)PL varied between 
0.3 and 3.3 microg ml(-1). Normalized concentration values showed a delayed
increase in c(P)G compared with c(P)PL under constant propofol infusion before
the onset of cardiopulmonary bypass, and a delayed decrease after stopping the
propofol at the end of anaesthesia. CONCLUSIONS: /st> Propofol can be measured in
exhaled gas from the beginning until the end of propofol anaesthesia. The
different time courses of c(P)PL and c(P)G have to be considered when
interpreting c(P)G.

Circulation. 2009 Mar 30. [Epub ahead of print]

Benefits and Risks of Corticosteroid Prophylaxis in Adult Cardiac Surgery. A
Dose-Response Meta-Analysis.

Ho KM, Tan JA.

Department of Intensive Care Medicine, Royal Perth Hospital, and School of
Population Health, University of Western Australia, Perth, Australia.

BACKGROUND: -Cardiopulmonary bypass and cardiac surgery are associated with a
significant systemic inflammatory response that may increase postoperative
complications. This meta-analysis assessed whether the benefits and risks of
corticosteroid use were dose dependent in adult cardiac surgery. Methods and
Results-Randomized controlled trials of the use of corticosteroid prophylaxis in 
adult cardiac surgery (>18 years of age) requiring cardiopulmonary bypass were
selected from MEDLINE (1966 to August 1, 2008), EMBASE (1988 to August 1, 2008), 
and the Cochrane controlled trials register without any language restrictions. A 
total of 3323 patients from 50 randomized controlled trials were identified and
subject to meta-analysis. Corticosteroid prophylaxis reduced the risk of atrial
fibrillation (25.1% versus 35.1%; number needed to treat, 10; relative risk,
0.74; 95% confidence interval [CI], 0.63 to 0.86; P<0.01) and length of stay in
the intensive care unit (weighted mean difference, -0.37 days; 95% CI, -0.21 to
-0.52; P<0.01) and hospital (weighted mean difference, -0.66 days; 95% CI, -0.77 
to -1.25; P=0.03) compared with placebo. The use of corticosteroid was not
associated with an increased risk of all-cause infection (relative risk, 0.93;
95% CI, 0.61 to 1.41; P=0.73), but hyperglycemia requiring insulin infusion after
corticosteroid prophylaxis was common (28.2%; relative risk, 1.49; 95% CI, 1.11
to 2.01; P<0.01). No additional benefits were found on all outcomes beyond a
total dose of 1000 mg hydrocortisone, and very high doses of corticosteroid were 
associated with prolonged mechanical ventilation. Conclusions-Evidence suggests
that low-dose corticosteroid is as effective as high-dose corticosteroid in
reducing the risk of atrial fibrillation and duration of mechanical ventilation
but with fewer potential side effects in adult cardiac surgery.

Pediatr Crit Care Med. 2009 Mar 25. [Epub ahead of print]

Children undergoing heart transplant are at increased risk for postoperative
vasodilatory shock.

Killinger JS, Hsu DT, Schleien CL, Mosca RS, Hardart GE.

From the Department of Pediatrics (JSK, CLS, GEH), Division of Critical Care
Medicine; Department of Pediatrics (DTH), Division of Cardiology; and Department 
of Surgery (RSM), Division of Cardiothoracic Surgery, Columbia University,
College of Physicians and Surgeons, Bronx, NY.

OBJECTIVE:: To determine the incidence of vasodilatory shock (VDS) in children
after cardiopulmonary bypass (CPB), and to describe this syndrome of post-CPB VDS
in children. DESIGN:: Prospective, observational. SETTING:: Pediatric and
neonatal intensive care units in a tertiary care, children's hospital. PATIENTS::
Three hundred children undergoing CPB. INTERVENTIONS:: None. MEASUREMENTS AND
MAIN RESULTS:: Three hundred subjects undergoing CPB were evaluated for clinical 
evidence of VDS following CPB. The incidence of post-CPB VDS was 3%.
Characteristics of children who developed VDS: higher peak lactate (6.2 +/- 2.6
vs. 3.0 +/- 2.1 mmol/L; p = 0.0002), higher peak serum BUN (18.5 +/- 4.6 vs. 15.6
+/- 7.2 mg/dL; p = 0.04), lower urine output (1.7 +/- 0.8 vs. 2.6 +/- 0.2
mL/kg/hr; p = 0.04), and fewer intensive care unit free days (14.9 +/- 9.0 vs.
21.1 +/- 7.2 days; p = 0.01). Univariate predictors for the development of
post-CPB VDS included children who had heart transplant (HT) (relative risk [RR],
9.8; 95% confidence interval [CI], 2.7-35.2) or ventricular assist device (VAD)
placed (RR, 17.9; 95% CI, 3.8-84.1), a cardiomyopathy diagnosis (RR, 8.5; 95% CI,
2.3-31), age >12 years (RR, 4.5; 95% CI, 1.2-17.0), CPB time >180 minutes (RR,
7.1; 95% CI, 1.9-26.2), and preoperative ventricular dysfunction (RR, 3.7; 95%
CI, 1.0-13.4). By stratified analysis, the only independent predictor for the
development of VDS was undergoing HT/VAD. CONCLUSIONS:: Post-CPB VDS is uncommon 
in children. However, children who undergo a HT or VAD placement are at high risk
for developing post-CPB VDS. Recognition that the overall incidence of post-CPB
is low-except in the HT/VAD population-may help guide therapy in the pediatric
post-CPB patient.

Crit Care Med. 2009 Mar 25. [Epub ahead of print]

Rivastigmine for the prevention of postoperative delirium in elderly patients
undergoing elective cardiac surgery-A randomized controlled trial*

Gamberini M, Bolliger D, Lurati Buse GA, Burkhart CS, Grapow M, Gagneux A,
Filipovic M, Seeberger MD, Pargger H, Siegemund M, Carrel T, Seiler WO, Berres M,
Strebel SP, Monsch AU, Steiner LA.

From the Department of Anesthesia (MG, DB, GALB, CSB, MF, MDS, HP, MS, SPS, LAS),
University Hospital Basel, Basel, Switzerland; Division of Cardiac Surgery (MG,
TC), University Hospital Basel, Basel, Switzerland; Memory Clinic (AG, AUM),
University Hospital Basel, Basel, Switzerland; Geriatric Unit (WOS), University
Hospital Basel, Basel, Switzerland; and RheinAhrCampus Remagen (MB), University
of Applied Sciences Koblenz, Remagen, Germany.

OBJECTIVE:: Cardiac surgery is frequently followed by postoperative delirium,
which is associated with increased 1-year mortality, late cognitive deficits, and
higher costs. Currently, there are no recommendations for pharmacologic
prevention of postoperative delirium. Impaired cholinergic transmission is
believed to play an important role in the development of delirium. We tested the 
hypothesis that prophylactic short-term administration of oral rivastigmine, a
cholinesterase inhibitor, reduces the incidence of delirium in elderly patients
during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind,
randomized, placebo-controlled trial. SETTING:: One Swiss University Hospital.
PATIENTS:: One hundred twenty patients aged 65 or older undergoing elective
cardiac surgery with cardiopulmonary bypass. INTERVENTION:: Patients were
randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral
rivastigmine per day starting the evening before surgery and continuing until the
evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS:: The
primary predefined outcome was delirium diagnosed with the Confusion Assessment
Method within 6 days postoperatively. Secondary outcome measures were the results
of daily Mini-Mental State Examinations and clock drawing tests, and the use of a
rescue treatment consisting of haloperidol and/or lorazepam in patients with
delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the
placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment
effect on the time course of Mini-Mental State Examinations and clock drawing
tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in
the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or 
lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine
groups, respectively. CONCLUSION:: This negative or, because of methodologic
issues, possibly failed trial does not support short-term prophylactic
administration of oral rivastigmine to prevent postoperative delirium in elderly 
patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Crit Care Med. 2009 Mar 25. [Epub ahead of print]

Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: 
Effects on interleukin-6 to interleukin-10 ratio and early outcome*

Weis F, Beiras-Fernandez A, Schelling G, Briegel J, Lang P, Hauer D, Kreth S,
Kaufmann I, Lamm P, Kilger E.

From the Departments of Anesthesiology (FW, GS, JB, PL, DH, SK, IK, EK) and
Cardiac Surgery (AB-F, PL), University of Munich, Klinikum Grosshadern, Munich,
Germany.

BACKGROUND:: Severe systemic inflammation (systemic inflammatory response
syndrome) associated with cardiac surgery often leads to a worse short-term and
long-term outcome. Stress doses of hydrocortisone have been successfully used to 
improve outcome of CS. The interleukin 6 (IL-6) to interleukin 10 (IL-10) ratio
is associated with outcome after trauma and major surgery. OBJECTIVE:: To
evaluate immunologic effects (especially IL-6 to IL-10 ratio) of stress doses of 
hydrocortisone in a high-risk group of patients after cardiac surgery with
cardiopulmonary bypass. DESIGN:: Prospective, randomized, double-blinded,
placebo-controlled trial. SETTING:: Cardiovascular intensive care unit of a
university hospital. PATIENTS:: High-risk patients (n = 36) undergoing CS.
INTERVENTION:: Stress doses of hydrocortisone or placebo. MAIN OUTCOME MEASURES::
IL-6 to IL-10 ratio and other markers of systemic inflammation at predefined time
points; short-term clinical outcome. RESULTS:: The two study groups did not
differ with regard to demographic data. The patients from the hydrocortisone
group (n = 19) had significantly lower levels of IL-6 and higher levels of IL-10,
resulting in an attenuated change in IL-6/IL-10 ratio (28.7 [6.4/128.7] vs. 292.8
[6.5/534.6] 4 hours after cardiopulmonary bypass; p < 0.001). Patients in the
hydrocortisone group had a shorter duration of catecholamine support (1 [1/2] vs.
4 [2/4.5] days; p = 0.02), a shorter length of stay in the intensive care unit (2
[2/3] vs. 6 [4/8] days; p = 0.001), and a lower incidence of postoperative atrial
fibrillation (26% vs. 59%; p = 0.04). CONCLUSIONS:: Stress doses of
hydrocortisone attenuate the evolution of IL-6/IL-10 ratio in patients with
systemic inflammatory response syndrome after CS, which seems to be associated
with an improved outcome. The immunologic effects of hydrocortisone may thus be
both, inhibitory (IL-6) and permissive (IL-10), regarding the immune response.

Eur J Cardiothorac Surg. 2009 Mar 19. [Epub ahead of print]

Thyroid function during coronary surgery with and without cardiopulmonary bypass.

Velissaris T, Tang AT, Wood PJ, Hett DA, Ohri SK.

Department of Cardiac Surgery, Wessex Cardiothoracic Centre, Southampton General 
Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom.

Objective: Cardiopulmonary bypass (CPB) is associated with thyroid hormone
changes consistent with euthyroid sick syndrome. Similar changes have been
observed after general surgical operations. Thyroid hormone changes and their
association with global oxygen consumption were studied in low-risk patients
undergoing coronary artery bypass grafting (CABG) with and without CPB. Methods: 
Fifty-two patients undergoing primary CABG by the same surgeon were randomised
into either on-pump (ONCAB, n=26) or off-pump (OPCAB, n=26) groups.
Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine
(fT3) levels were measured at sequential time-points using chemiluminescence
assays. Global oxygen consumption was measured at sequential time-points using a 
continuous cardiac output Swan-Ganz catheter. Results: In both groups TSH and fT4
remained within normal range throughout the study. There was a similar and
progressive decline in fT3 levels with no significant difference between the
groups over time (p=0.42). Mean fT3 levels at 24h were below the normal range and
significantly lower than baseline values (ONCAB, 3.3+/-0.69pmol/L vs
5.1+/-0.41pmol/L, p<0.001; OPCAB, 3.3+/-0.51pmol/L vs 5.0+/-0.46pmol/L, p<0.001).
There was a significant inverse relationship between fT3 levels and global oxygen
consumption. Conclusions: Off-pump surgery is associated with thyroid hormone
changes similar to conventional surgical revascularisation. The data suggest that
further studies into T3 administration during OPCAB may be warranted.

J Cardiothorac Vasc Anesth. 2009 Mar 18. [Epub ahead of print]

Evaluation and Comparison of Early Hemodynamic Changes After Elective Mitral
Valve Replacement in Patients With Severe and Mild Pulmonary Arterial
Hypertension.

Tempe DK, Hasija S, Datt V, Tomar AS, Virmani S, Banerjee A, Pande B.

Department of Anaesthesiology and Intensive Care, New Delhi, India.

OBJECTIVE: To evaluate and compare early hemodynamic changes after elective
mitral valve replacement (MVR) in patients with severe and mild pulmonary
arterial hypertension (PAH). DESIGN: A prospective observational study. SETTING: 
University-affiliated hospital. PARTICIPANTS: Sixty patients undergoing elective 
MVR. INTERVENTIONS: The patients were divided into 2 equal groups based on the
presence (group A) or absence (group B) of severe PAH defined as systolic
pulmonary artery pressure (PAP) >/=50 mmHg on preinduction pulmonary artery
catheterization. Thiopental, fentanyl, midazolam, isoflurane, and rocuronium (or 
vecuronium if the heart rate >100 beats/min) were used for the induction and
maintenance of anesthesia. MVR was performed using standard cardiopulmonary
bypass (CPB) techniques. The therapy for PAH was electively instituted in all
patients with a nitroglycerin infusion (0.5-1 mug/kg/min), deliberate hypocarbia 
(arterial carbon dioxide tension 

Eur J Anaesthesiol. 2009 Mar 7. [Epub ahead of print]

Predictors of prolonged mechanical ventilation in a cohort of 5123 cardiac
surgical patients.

Cislaghi F, Condemi AM, Corona A.

aCardiac Anaesthetic Department, Azienda Ospedaliera Luigi Sacco, Milano-Polo
Universitario, Milan, Italy bCentre for Intensive Care Medicine and Bloomsbury
Institute of Intensive Care Medicine, University College London, London, UK cICU 
Department, Azienda Ospedaliera Luigi Sacco, Milano-Polo Universitario, Milan,
Italy.

BACKGROUND: Prolonged mechanical ventilation (PMV) after heart surgery is
associated with increased patient morbidity and mortality. METHODS: In this
prospective observational cohort study the aim was to assess PMV predictors and
its impact on ICU, hospital length of stay and survival in cardiac surgical
patients admitted to our eight-bed ICU from January 2000 to December 2006. All
perioperative patient variables were put into an electronic database. Five
thousand one hundred and twenty-three patients were divided into two cohorts:
early extubation, undergoing a successful extubation for 12 h or less, and
delayed extubation, needing a mechanical ventilation for more than 12 h. RESULTS:
A logistic regression model identified the following as PMV predictors: age more 
than 65 years [odds ratio (OR), 1.296; 95% confidence interval (CI), 1.017-1.069;
P = 0.016], chronic renal failure (OR, 1.571; 95% CI, 1.566-2.466; P = 0.011),
chronic obstructive pulmonary disease (OR, 1.453; 95% CI, 1.695-2.454; P =
0.006), redo surgery (OR, 2.010; 95% CI, 1.389- 2.114; P = 0.001), emergency
surgery (OR, 1.622; 95% CI, 1.515-2.494; P = 0.016), New York Heart
Association/Canadian Cardiovascular Society class higher than 2 (OR, 1.491; 95%
CI, 1.704-2.321; P = 0.001), left ventricular ejection fraction of 30% or less
(OR, 2.125; 95% CI, 1.379-1.991; P = 0.000), red blood cell (OR, 5.430; 95% CI,
3.636-8.130; P = 0.000) and fresh frozen plasma transfusion units more than four 
(OR, 3.019; 95% CI, 1.808-5.050; P = 0.000) and cardiopulmonary bypass time more 
than 77 min (OR, 2.030; 95% CI, 1.248-2.174; P = 0.002). Early extubation group
patients showed a higher probability of being discharged from ICU to cardiac
surgical ward (log-rank = 1108.951; P = 0.000) and from cardiac to rehabilitation
ward (log-rank = 598.005; P = 0.000) and higher hospital survival (log-rank =
53.215; P = 0.000). CONCLUSION: This review allowed us to assess predictors,
helping us to identify 'a priori' patients more likely to undergo PMV.

Eur J Cardiothorac Surg. 2009 Mar 7. [Epub ahead of print]

Mid-term results of right axillary incision for the repair of a wide range of
congenital cardiac defects.

Dave HH, Comber M, Solinger T, Bettex D, Dodge-Khatami A, Prêtre R.

Department of Congenital Cardiac Surgery, University Children's Hospital Zurich, 
Steinwiesstrasse 75, 8032 Zurich, Switzerland.

Objective: We evaluated the mid-term results of the right axillary incision used 
for the repair of various congenital heart defects. Methods: All the patients who
were operated with this incision between March 2001 and December 2007 were
reviewed. There were 123 patients (median age 4.7 {0.4-19.4} years and median
weight 16.6 {3.8-62} kg) undergoing atrial septal defect (ASD) closure (62),
repair of partial anomalous pulmonary venous connection (PAPVC) (22), correction 
of partial atrioventricular septal defect (AVSD) (19), and restrictive
perimembranous ventricular septal defect (VSD) (20). Additional procedures
involved tricuspid valve plasty (10), mitral annuloplasty (3), reduction plasty
of the aortic sinus (2), resuspension of the aortic valve cusp (2), sub aortic
membrane resection (1), or reimplantation of Scimitar vein (1). The surgical
technique involved peripheral (groin) and central (SVC+/-aorta) cannulation for
institution of cardiopulmonary bypass. Fibrillatory arrest was used for repair of
ASDs and cardioplegic arrest for repairs involving the atrioventricular valves as
well as VSDs. The median CPB and aortic clamp times were 72 (35-232) and 0
(0-126) min, respectively. Results: There was no need for conversion to another
approach in any patient. Early morbidity included transient paresis of left upper
arm (1), stenting of SVC after repair of a sinus venosus defect (1) and revision 
for bleeding (1). Follow-up echo showed no residual defect in 116 patients and
minor residual defects in 7 patients: tiny ASD (2), tiny VSD (1) and mitral
regurgitation (4). One patient developed stenosis in the right external iliac
artery used for cannulation, necessitating surgical intervention. All the
patients are in excellent condition after a median follow-up of 4.1 (0.4-7.1)
years. The incision healed well and the thorax and the breast showed no deformity
on follow-up. Conclusions: The right axillary incision provides a quality of
repair for various congenital defects similar to that obtained by using standard 
surgical approaches. Because of its deceitful location, and the camouflaging
effect of being hidden by the resting arm, it has superior cosmetic appeal
compared to conventional incisions. The incision does not interfere with
subsequent development of the thorax or the breast (in case of females).

Crit Care Med. 2009 Mar;37(3):902-11.

Pulsatile perfusion with intra-aortic balloon pumping ameliorates whole body
response to cardiopulmonary bypass in the elderly.

Onorati F, Santarpino G, Presta P, Caroleo S, Abdalla K, Santangelo E, Gulletta
E, Fuiano G, Costanzo FS, Renzulli A.

Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Catanzaro, Italy.
frankono@libero.it

OBJECTIVE: The growing life expectancy has led the elderly to be increasingly
referred to coronary artery bypass grafting. Preexisting comorbidities may
benefit from theoretical advantages of pulsatile perfusion during cardiopulmonary
bypass (CPB). DESIGN: Prospective randomized trial. SETTING: Cardiac surgery unit
in a university hospital. PATIENTS: Eighty consecutive patients older than 70
years. INTERVENTIONS: Elective coronary artery bypass grafting on CPB,
randomizing to conventional linear CPB (40 patients, group A) or intra-aortic
balloon pump (IABP)-induced pulsatile CPB (40 patients, group B). MEASUREMENTS
AND MAIN RESULTS: We evaluated hemodynamic response by pulmonary artery flotation
catheter, metabolic/splanchnic response by lactate and transaminase, bilirubin,
amylase, and renal function (creatinine clearance, creatinine, incidence of renal
insufficiency and failure), respiratory response by Pao2/Fio2, respiratory
compliance, scoring of chest radiograph, intubation time, and need for
noninvasive positive-pressure ventilation, hematologic response by chest
drainage, hemocoagulative and fibrinolytic cascades, and transfusions.
IABP-related complications were recorded. Two minor IABP-related complications
(2.5%) were registered. Hemodynamics was comparable, except for a slightly better
cardiac index and indexed systemic vascular resistances at the end of CPB and at 
intensive therapy unit (ITU) admission (p < 0.05). Transaminases, bilirubin,
amylase, proved lower in group B (p < 0.05 from ITU admission to 48 hours).
Creatinine clearance, serum creatinine, and lactate were better in group B (p <
0.05), and acute renal insufficiency was accordingly lower (p = 0.02).
Respiratory response demonstrated better Pao2/Fio2 and respiratory compliance
from aortic declamping to 48 hours, with better scoring of chest radiograph (p < 
0.05 from ITU admission to 48 hours), lower noninvasive positive-pressure
ventilation (p = 0.002) and intubation time (p = 0.031) in group B. Lower chest
drainage (p < 0.05 at first and second day), transfusions (p < 0.05), activated
partial thromboplastin time, international normalized ratio, white blood cells,
and D-dimer (p < 0.05 from ITU admission to 48 hours), together with higher
platelets, fibrinogen, and antithrombin III (p < 0.05 from ITU admission to 48
hours) were demonstrated in the pulsated group. CONCLUSIONS: IABP-induced
pulsatile flow significantly improves whole body perfusion in the elderly
undergoing CPB.