Reducing the risk of major elective
surgery: randomised controlled trial of preoperative optimisation of
oxygen delivery. Wilson J, Woods I, Fawcett J et al. Br Med J
1999; 318: 1099-1103.
In the United Kingdom, most patients are taken directly
from the general ward to the operating theatre before major elective
surgery. The extent of peri-operative monitoring is variable and the site
of post-operative care will depend on the premorbid state and the
availability of ITU or HDU beds. Optimisation of oxygen delivery has been
shown to improve the outcome of high-risk patients undergoing major
surgery. This can be achieved by the use of intravenous fluids and
inotropic agents. The aim of this study was to determine whether
preoperative optimisation of oxygen delivery improved post-operative
outcome and to determine whether the inotropic agents, adrenaline and
dopexamine, had similar effects. The study was performed as randomised
controlled trial in a district general hospital. In total 138 patients
undergoing major elective surgery (aneurysm surgery, upper GI or anterior
resections, cystectomy) and at risk of developing post-operative
complications because of coexisting disease states were randomised into
three groups. Two groups received invasive haemodynamic monitoring, fluid
and either adrenaline or dopexamine to increase oxygen delivery. The third
(control) group received routine peri-operative care. The main outcome
measures were hospital morbidity and mortality. Overall, 3/92 (3%)
preoptimised patients died compared with 8/46 (17%; p=0.007) in
the control group. There was no difference in mortality between the
treatment groups, but 14/46 (30%) in the dopexamine group developed
complications compared with 24/46 (52%) in the adrenaline group and 28/46
(61%) in the control group. The use of dopexamine was associated with a
decreased hospital stay. It was concluded that routine pre-operative
optimisation of patients undergoing major surgery resulted in a
significant improvement in peri-operative care.
E5 murine monoclonal antiendotoxin
antibody in gram-negative sepsis. Angus D C, Birmingham M C, Balk R
A et al. JAMA 2000; 283: 1723-1730.
Despite improvements in intensive care medicine and an
increased understanding of the pathophysiology of gram-negative sepsis,
over the last 20 years the overall mortality of this condition has failed
to improve. Endotoxin is believed to play a central role in the
pathophysiology of gram-negative sepsis. Encouraging results from
animal studies has lead to large-scale clinical trials of immunomodulatory
therapies in septic patients. One such approach has been the use of
monoclonal antibodies directed against endotoxin. The results of
clinical studies published to date have been disappointing. The aim
of this study was to assess the efficacy and safety of E5, a murine
monoclonal anti-endotoxin IgM antibody, in patients with gram-negative
sepsis. A multicentre double-blind, randomised placebo-controlled trial was
conducted in 136 US intensive care units. Patients with clinical
features of severe sepsis and documented or probable gram-negative
infection were randomised to either two doses of E5 monoclonal antibody
(n=550) or placebo (n=552). The primary end-point was mortality at
14 days. Secondary end-points were 28-day mortality, adverse events
and mortality in subgroups presenting without clinical evidence of shock.
The trial was stopped after the second interim analysis as there was no
significant difference in mortality between the two treatment groups (30%
vs. 31%. p=0.67). There was a similar profile of adverse events
between the two groups. It was concluded that despite adequate
sample size and a high enrolment rate of patients with confirmed
gram-negative sepsis, E5 did not improve the short-term survival.
Current study rationale and design should be carefully reviewed before
further large-scale studies of patients with sepsis are conducted.
Effects of maximizing oxygen delivery on
morbidity and mortality in high-risk surgical patients. Lobo S M,
Salgado P F, Castillo V G T et al. Crit Care Med 2000;
Surgical patients on the intensive care unit frequently
have a postoperative period complicated by sepsis, systemic inflammatory
response syndrome and organ dysfunction. Such patients have often
had episodes of haemodynamic instability during the perioperative period.
A correlation between oxygen debt in the intraoperative and early
postoperative period and the evolution of organ failure and death has been
previously demonstrated. Survival of high risk patients may be
related to supranormal increases in cardiac index and oxygen delivery.
The aim of the present study was to assess the effect of maximizing oxygen
delivery on morbidity and mortality in patients over the age of 60 years
with chronic disease undergoing major elective surgery. A
prospective randomised study of 37 high-risk patients undergoing major
surgery was performed. The haemodynamic and oxygen transport
variable and outcome in 18 patients (protocol group) treated to maintain
normal oxygen delivery were compared with 19 patients (control group)
treated to maintain 'supranormal' values. Therapy in both groups
consisted of volume expansion and, when necessary, the use of dobutamine
for the first 24 hours after surgery. The study was terminated early
because of a significant difference in 60-day mortality between the two
groups (9/18 (50%) vs. 3/19 (16%) p<0.05). The prevalence of of
clinical and infectious complications was higher in the control group.
It was concluded that older patients with pre-existing cardiorespiratory
disease undergoing major surgery had a reduced mortality and lesser
morbidity when dobutamine was utilised to maximize oxygen transport.
Complications of femoral and subclavian
venous catheterization in critically ill patients. Merrer J,
De Jonghe B, Golliot F et al. JAMA 2001; 286:
Central venous catheterisation is often necessary to treat
critically ill patients in intensive care units (ICU). However, the
procedure can lead to serious and occasionally life-threatening
complications. The choice of insertion site can influence the the
incidence and type of such complications. These can be mechanical
(e.g. haematoma, pneumothorax, arterial puncture), infections (site or
systemic infection) or thrombotic (partial or complete vessel occlusion).
The aim of this study was to compare the mechanical, infectious and
thrombotic complications of femoral and subclavian catheterisation in the
setting of a randomised controlled trial. Between December 1997 and
July 2000 in 8 ICUs, 289 adult patients receiving a first central venous
catheter were randomised to under go either femoral (n=145) or subclavian
(n=144) line insertion. The rate and severity of complications were
compared. Femoral catheterisation was associated with a higher
overall incidence of infectious complications and of major infectious
complications as well as of overall thrombotic complications and complete
vessel thrombosis. The rate of overall and major mechanical
complications were similar between the two groups. Risk factors for
mechanical complications were duration of insertion and insertion during
the night. The only factor associated with infectious complications
was femoral catheterisation. Antibiotic administration via the
catheter decreased the risk of infectious complications. Femoral
catheterisation was the only risk factor for thrombotic complications.
It was concluded that femoral venous catheterisation is associated with a
greater risk of infectious and thrombotic complications than subclavian
catheterisation in ICU patients.
Early goal-directed therapy in the
treatment of severe sepsis and septic shock. Rivers E, Nguyen
B, Havstad S et al. N Eng J Med 2001; 345:
Severe sepsis and septic shock are characterised by
circulatory abnormalities including intravascular volume depletion,
peripheral vasodilatation, myocardial depression and increased metabolism
leading to an imbalance between systemic oxygen delivery and oxygen
demand. This results in global tissue hypoxia and shock. These
physiological derangements frequently occur in septic patients on wards
and in emergency departments. Goal-directed therapy is commonly used in
the management of severe sepsis and septic shock within the intensive care
unit (ICU). This approach involves adjustments of cardiac preload,
afterload and contractility to achieve a balance between oxygen delivery
and demand. The aim of this study was to evaluate the efficacy of early
goal-directed therapy before admission to the ICU. Patients admitted to an
emergency department with severe sepsis or septic shock were randomly
assigned to either six hours of goal-directed therapy or standard therapy
prior to admission to the ICU. Clinicians who subsequently assumed the
care of the patient were blinded to the treatment assignment within the
emergency department. The primary end-point was in-hospital mortality.
Secondary end-points with respect to resuscitation and APACHE II scores
were also measured for 72 hours. Of the 263 patients enrolled, 130 were
randomised to early goal-directed therapy and 133 to standard therapy.
There was no difference between the groups with regard to baseline
characteristics. In-hospital mortality was 31% in the early goal-directed
therapy group and 47% in the standard therapy group (p=0.009). During the
study period patients receiving goal-directed therapy had a higher mean
central venous oxygen saturation and a lower arterial lactate and base
deficit. Mean APACHE II scores were significantly lower in early
goal-directed therapy group (p<0.001). It was concluded that early
goal-directed therapy provides significant benefits with respect to
outcome in patients with severe sepsis and septic shock.
Effects of selective decontamination of
digestive tract on mortality and acquisition of resistant bacteria in
intensive care: a randomised controlled trial. de Jonge E,
Schultz M J, Spanjaard L et al. Lancet 2003; 362:
Nosocomial infections contribute substantially to
morbidity and mortality of patients treated in intensive care units.
Most of these infections are thought to be preceded by oropharyngeal and
intestinal colonisation with pathogenic microorganisms. Selective
decontamination of the digestive tract (SDD) is an infection-prevention
regime aimed at reducing the incidence and consequences of nosocomial
infection. The aim of this study was to assess the effect of SDD on
intensive care unit (ICU) and hospital mortality and on the acquisition of
resistant bacteria in adult patients admitted to intensive care. The
study was a prospective randomised uncontrolled clinical trial of 934
patients admitted to a medical and surgical intensive care unit.
Patients were randomly assigned to either enteral polymyxin E, tobramycin
and amphotericin B combined with an initial 4-day course of intravenous
cefotaxime (n = 466) or standard treatment (n = 468). The primary
endpoints were ICU and hospital mortality and the acquisition of resistant
bacteria. In the SDD group 69 (15%) patients died in the ICU
compared with 107 (23%) in the control group (p = 0.002).
Hospital mortality was lower in the SDD group than in the control group
(113 vs. 146. p = 0.02). During their stay in intensive
care, colonisation with gram-negative bacteria resistant to ceftazidime,
ciprofloxacin, imipenem, polymyxin E or tobramycin occurred in 61 (16%) of
the 378 SDD patients and in 104 (26%) of the 395 patients in the control
group (p = 0.001). No patient in either group was colonised
with methicillin-resistant Staphylococcus aureus. It was concluded
that in a setting with low prevalence of vancomycin-resistant enterococcus
and MRSA, SDD can decrease ICU and hospital mortality and colonisation
with resistant gram-negative aerobic bacteria.
Perioperative beta-blocker therapy and
mortality after major noncardiac surgery. Lindenauer P K,
Pekow P, Wang K et al. N Engl J Med 2005; 353:
More than 20 million operations are performed annually at
hospitals throughout the United States and although advances in operative
and anaesthetic techniques have reduced the risks, some 1 in 10 patients
can be expected to have a complication within 30 days of major surgery.
Postoperative cardiovascular complications are associated with significant
risk of other complications and death. Despite limited evidence from
randomised trials, perioperative treatment with beta-blockers is now
widely advocated. The aim of this study was to assess the use of
perioperative beta-blockers and their association with in-hospital
mortality in routine clinical practice. A retrospective cohort study
was undertake of patients 18 years of age or older who underwent major
non-cardiac surgery in 2000 and 2001 at 329 hospitals through out the
United States. Propensity-score matching was used to adjust for
differences between patients who received perioperative beta-blockers and
those who did not receive such therapy. In-hospital mortality was
compared using multivariable logistic modelling. Of 782,969 patients
85% had no recorded contraindication to beta-blockers of whom 18% received
such treatment during the first two hospital days, including 14% patients
with a Revised Cardiac Risk Index (RCRI) of 0 and 44% with a score of 4 or
higher. The relationship between perioperative beta-blocker
treatment and risk of death varied directly with cardiac risk. In
patients with RCRI score of 2,3,4 or more, the adjusted odds ratio for
death in hospital were 0.88 (95% CI 0.80.0.98), 0.71 (95% CI 0.63-0.80)
and 0.58 (95% CI 0.50-0.67) respectively. It was concluded that
perioperative beta-blocker therapy is associated with a reduced risk of
in-hospital death amongst high-risk but not low-risk patients undergoing
major noncardiac surgery. Patient safety maybe enhanced by
increasing the use of beta-blockers in high-risk patients.
Randomised clinical trial assessing the
effect of Doppler-optimized fluid management on the outcome after elective
colorectal resection. Noblett S E, Snowden C P, Shenton
B K et al. Br J Surg 2006; 93: 1069-1076.
Recent developments in multimodal care and enhanced
surgical recovery programmes after elective colorectal surgery have
identified potential improvements in outcome after major bowel resection.
The role of perioperative fluid management remains under debate.
Various fluid management regimes have been proposed with the aim to avoid
tissue hypoperfusion and activation of the systemic inflammatory response.
Oesophageal doppler monitoring is a minimally invasive method of
accurately determining haemodynamic status in the perioperative period.
Accurate guidance of intraoperative fluid administration using oesophageal
doppler monitoring may reduce the risk of perioperative hypovolaemia.
The aim of this study was to assess whether protocolized fluid
administration using oesophageal doppler may improve the postoperative
outcome in patients undergoing elective colorectal surgery. A total
of 108 patients were recruited into a double-blind prospective randomised
controlled trial. An oesophageal doppler probe was placed in all
patients. The control group received perioperative fluid at the
discretion of the anaesthetist, whereas the intervention group received
additional colloid boluses based on doppler assessment. Primary
outcome was length of postoperative hospital stay. Secondary
outcomes were morbidity, return of gastrointestinal function and cytokine
markers of the systemic inflammatory response. Standard preoperative
and postoperative management was used in all patients. Demographic
and surgical details were similar in the two groups. Aortic flow
time, stroke volume, cardiac output and cardiac index during the
intraoperative period was higher in the intervention group (p<0.05).
The intervention group had a reduced postoperative stay (7 vs. 9 days.
p=0.005), fewer intermediate or major postoperative complications (2
vs. 15. p=0.043) and tolerated diet earlier (2 vs. 4 days. p=0.029).
There was a reduced rise in perioperative level of the cytokine
interleukin 6 in the intervention group (p=0.039). It was
concluded that a protocol based fluid optimization programme using
intraoperative oesophageal doppler monitoring leads to a shorter hospital
stay and decreased morbidity in patients undergoing elective colorectal
Comparison of dopamine and norepinephrine in the treatment
of shock. De Backer D, Biston P, Devriendt J et al.
N Eng J Med 2010; 362: 779-789.
Both dopamine and norepinephrine are recommended as first-line
vasopressor agents in the treatment of shock. There is a continuing
controversy about whether one agent is superior to the other. In this
multicentre, randomized trial, patients with shock were asigned to receive
either dopamine or norepinephrine as first-line vasopressor therapy to
restore and maintain blood pressure. When blood pressure could not be
maintained with a dose of 20 µg per kilogram of body weight per minute for
dopamine or a dose of 0.19 µg per kilogram per minute for norepinephrine,
open-label norepinephrine, epinephrine, or vasopressin could be added. The
primary outcome was the rate of death at 28 days after randomization.
Secondary end points included the number of days without need for organ
support and the occurrence of adverse events. The trial included 1679
patients, of whom 858 were assigned to dopamine and 821 to norepinephrine.
The baseline characteristics of the groups were similar. There was no
significant between-group difference in the rate of death at 28 days
(52.5% in the dopamine group and 48.5% in the norepinephrine group; odds
ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10).
However, there were more arrhythmic events among the patients treated with
dopamine than among those treated with norepinephrine (207 events [24.1%]
vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that
dopamine, as compared with norepinephrine, was associated with an
increased rate of death at 28 days among the 280 patients with cardiogenic
shock but not among the 1044 patients with septic shock or the 263 with
hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock,
and P=0.84 for hypovolemic shock, in Kaplan–Meier analyses). It was
concluded that although there was no significant difference in the rate of
death between patients with shock who were treated with dopamine as the
first-line vasopressor agent and those who were treated with
norepinephrine, the use of dopamine was associated with a greater number
of adverse events.