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12
Prophylactic and Therapeutic
Antibiotics in Surgery
Antibiotic prophylaxis
Choice of antibiotic
SU6.2: Enumerate prophylactic and therapeutic antibiotics.
Plan appropriate management.
INTRODUCTION
Antibiotics are indicated for use in a surgical patient
either to prevent infection (prophylactic) or to treat an
established infection (therapeutic). Empirical antibiotics
means antibiotics which are used to treat clinically
suspected infections till culture and sensitivity reports
are available. Before the days of antibiotics almost every
surgery was infected, and the mortality rates were
very high. The discovery of penicillin in 1928 by Sir
Alexander Fleming changed the world of medicine.
Every patient who undergoes in-patient surgery will
have prophylactic antibiotics. Prophylactic antibiotics
depend upon the type of most probable organisms
which may colonise after a particular surgery. One
example is the use of gentamicin for potential
contamination that can happen during division of the
cystic duct during laparoscopic cholecystectomy.
Common Organisms in Surgical Site Infections
• Staphylococcus aureus
• Staphylococcus epidermidis
• Aerobic streptococci
• Anaerobic cocci
ANTIBIOTIC PROPHYLAXIS
Prophylactic antibiotics are most used to prevent infection of the surgical site.
Therapeutic antibiotics
Classification of antibiotics
It is important to note that only infection of the
surgical incision is prevented, and it does not prevent
other nosocomial infections.
Antibiotic prophylaxis is indicated in clean contaminated and contaminated operations. In clean surgeries,
antibiotics are only indicated in case of prosthetic
implants such as orthopaedic surgeries. Other clean
surgeries such as breast or hernia operations,
evidence has shown that antibiotic prophylaxis is not
required.
Most of the surgical site infections are caused by
endogenous gram-positive cocci that reside on the
skin of the patient. Infection from exogenous sources
such as health care workers or cross-contamination
from other patients reflects poor hospital standards
and strict action should be taken to prevent such
infections.
Antibiotics must be administered preoperatively,
1 hour before the skin incision is made, in order to attain
maximum blood and tissue concentrations before
bacterial growth can become established. However,
vancomycin and levofloxacin, if these drugs are used
for prophylaxis, have to be administered within
120 minutes of the procedural incision due to longer
administration times. In case of long duration surgeries,
or in surgeries with excessive blood loss, a repeat dosing
will be required, usually at 4 hourly intervals, to
maintain the desired tissue levels.
Unnecessary prolonged usage of prophylactic antibiotics is potentially harmful and increases the risk of
other nosocomial infections.
Everyone should know commonly used antibiotics,
mechanism of action and their coverage (Table 12.1).
44
Prophylactic and Therapeutic Antibiotics in Surgery
45
Table 12.1
Antibiotic class Mechanism of action Coverage
Penicillin Inhibit cell wall synthesis Gram-positive
Aminopenicillin, e.g. ampicillin, amoxicillin Inhibit cell wall synthesis Staphylococci, streptococci, E. coli,
1st gen cephalosporins, e.g. cefazolin, Inhibit cell wall synthesis Gram-positive, few gram-negative
cephalexin
2nd gen cephalosporins, e.g. cephotetan, Inhibit cell wall synthesis Gram-positive, few gram-negative and
cefoxitin anaerobes
3rd gen cephalosporins, e.g. ceftriaxone, Inhibit cell wall synthesis Gram-negative predominantly. Ceftazidime
cefaperazone, ceftazidime is also active against Pseudomonas
4th gen cephalosporins, e.g. cefepime Inhibit cell wall synthesis Gram-negative and few gram-positive
Aminopenicillin with beta lactamase Inhibit cell wall synthesis Gram-positive, gram-negative and
inhibitors, e.g. piperacillin tazobactam anaerobic
Carbapenems, e.g. ertapenem, imipenem Inhibit cell wall synthesis Gram-positive, gram-negative, and
meropenem anaerobic anti-pseudomonal
Fluoroquinolones, e.g. ciprofloxacin, Inhibit bacterial DNA synthesis by Gram-negative anti-pseudomonal
levofloxacin inhibiting DNA gyrase
Aminoglycosides, e.g. gentamicin, amikacin Inhibit bacterial protein synthesis by Gram-negative anti-pseudomonal
Lincosamide, e.g. clindamycin Inhibit bacterial protein synthesis by Gram-positive, anaerobic, active against
Glycopeptides, e.g. vamcomycin Inhibit cell wall synthesis Gram-positive. Active against MRSA
Antimetabolites, e.g. trimethoprim- Interfere with bacterial folic acid Gram-positive, negative. Active against
sulphamethoxazole synthesis MRSA
Nitroimidazole, e.g metronidazole Cause DNA damage Anaerobic
Commonly used antibiotics, mechanism of action and their coverage
Proteus
binding to 30S ribosomal subunit
binding to 50S ribosomal subunit MRSA
Choice of Antibiotic
As most of the SSIs are caused by gram-positive cocci
like Staphylococcus aureus, coagulase negative
Staphylococcus, etc., prophylactic antibiotics directed
against these are used for clean and clean contaminated
cases such as elective biliary and gastric surgeries
(Key Box 12.1). The recommended antibiotic is a firstgeneration cephalosporin such as cefazolin. An
alternative in patients with penicillin allergy is
clindamycin. In cases which require a gram-negative
or anaerobic coverage, either a second-generation
cephalosporin can be used, or a first-generation
cephalosporin with metronidazole is another choice.
In cases of emergencies, such as necrotising soft tissue
infections that require debridement or perforation
peritonitis with gross intra-abdominal contamination
that require exploratory laparotomy, the antibiotic used
for prophylaxis is continued as the therapeutic drug
even after the surgery. It is better to use the term
empirical antibiotics than prophylactic antibiotics in this
type of situation. Once the culture sensitivity pattern is
available, antibiotics are changed accordingly.
Key Box 12.1
Prophylactic Antibiotics
The antibiotic should have a narrow spectrum of
coverage of the relevant organisms that are prevalent
in causing surgical site infection—which depends on
the site and type of surgery.
The same antibiotic should not be a part of the
therapeutic regimens for infection as it may lead to
induction of resistance.
Should be administered 1 hour before surgery and
should be stopped within 24 hours after surgery—
ideally single dose.
Should be safe.
THERAPEUTIC ANTIBIOTICS
In cases of established infection, the use of antibiotics is
therapeutic, to eradicate the organism causing the infection. To choose appropriate antibiotics, it is important
to identify the causative organism and determine its
sensitivity pattern, to tailor treatment and avoid the
emergence of resistant strains.
Section I • Basic Principles of Surgery
46
Manipal Manual of Surgery
It should be kept in mind that antibiotic treatment
does not replace surgical treatment, and it is just an
adjunct to proper surgical drainage and eradication of
infection. In a case of simple peritonitis—example acute
appendicitis without shock, antibiotics are given for 5
to 7 days. However, in cases of peritonitis and shock
due to appendicular perforations, antibiotics may have
to be given for 10 to 14 days. More details are given in
the Chapter 45 on peritonitis.
Antibiotic therapy can be started empirically as soon
as a diagnosis of surgical infection is made, and the
choice of antibiotic depends on the most common
organisms suspected to cause the infection (Key Box 12.2).
Prior to starting empirical antibiotics, it is important to
collect pus or tissue samples from the wound, to be sent
for cultures, so that the organism can be identified,
sensitivity pattern can be obtained, and accordingly we
can modify the choice of antibiotic, if necessary.
Key Box 12.2
Therapeutic Antibiotics
Choose appropriate antibiotics based on culture and
sensitivity pattern of the organism.
Avoid overdosing and inappropriate combinations.
Educate patients to avoid self-prescribing antibiotics.
Stop treatment with antibiotics as soon as infection
subsides.
Adopt antibiotic stewardship programmes in hospitals
and increase awareness among all doctors.
There are two approaches to choosing therapeutic
antibiotics—narrow-spectrum coverage, which treats a
known infection when the sensitivity pattern of the
organism is available; or broad-spectrum coverage,
when the organism is not known and complete grampositive, gram-negative, and anaerobic coverage is
required, e.g. in patients with perforation peritonitis,
we can start a 3rd generation cephalosporin such as
cefoperazone along with metronidazole. Examples:
Cefazolin, vancomycin, and gentamicin. For patients
receiving cefazolin, 2 g is the current recommended dose
except for patients weighing greater than or equal to
120 kg, who should receive 3 g.
Once the sensitivity pattern of the organism is
available, then the antibiotic treatment can be deescalated, if the patient is improving. If there is no
clinical response to antibiotics, then a thorough review
of the patient must be done, as there might be an
underlying persistent infection that might need to be
drained surgically, or a new infection might have
developed.
Please note: The various infections and their treatment
have been given in the respective chapters. For example,
breast abscess—antibiotics MRSA, etc. in Chapter 39 on
breast. In the same fashion, details about antibiotics can
be got from other chapters such as skin, peritonitis,
intestinal obstruction, etc.
Some common infections, causative organisms and
antibiotic treatment are given in Table 12.2.
Table 12.2 Common infections, organisms, antibiotics and treatment plan
Disease Organisms Antibiotics Treatment
1. Boil/carbuncle/breast
abscess/parotid abscess
2. Necrotising fasciitis
3. Intra-abdominal perforations/
infections/peritonitis
4. Severe sepsis/peritonitis
5. Gas gangrene
Section I • Basic Principles of Surgery
Staphylococcus aureus
Streptococci, Staphylococcus
aureus, gram-negative orga-
nisms
Enterococci, gram-negative
organisms, anaerobic
organisms streptococci,
Staphylococcus aureus
Enterococci, gram-negative
organisms, anaerobic
organisms, streptococci,
Staphylococcus aureus
Clostridial organisms
Cloxacillin, clindamycin,
vancomycin
Cephalosporins
Amikacin
Cephalosporins
Amikacin
Metronidazole
Piperacillin and tazobactam
combination with metronidazole
Vancomycin and tazobactam
or a carbapenem or ceftriaxone with metronidazole.
Penicillin and clindamycin are
the other drugs
Antibiotics, incision and
drainage/excision
Antibiotics and early
aggressive debridement
Treatment of the source of
infection—suturing, removal
of organ or drainage of pus
Treatment of the source of
infection—suturing, removal
of organ or drainage of pus
Early antibiotics
Emergency debridement
Hyperbaric oxygen
13
Day Case/Care Surgery
Types of care
Type of surgery facilities
Selection criteria
SU11.4: Enumerate the indications and principles of day care
general surgery.
INTRODUCTION
Day care surgery is a term applied to performing a
surgical procedure as a day case. This provides advantages to both patients and healthcare providers. It causes
less disruption to the patient’s daily situation and contributes to financial savings to the hospital. It is an integral
component of healthcare delivery in resource-rich
countries, whereas in resource-poor countries, it is on
the rising trend due to increasing popularity. There
should be a team comprising of surgeon, anaesthetist,
floor managers, operational managers and nursing staff.
• In India day case/care surgery is gaining popularity
in cities. However, more than 70–80% population is
in rural India. Most of these patients come late to the
hospital and often they are illiterate. Hence the day
case surgery is currently limited to urban patients in
India.
Definitions
• Day surgery: Admitted and discharged within the
12-hour day.
• Overnight stay: 23-hour admission with early
morning discharge.
• Short-stay surgery: Admission of up to 72 hours.
Indications for Day Care Surgery
• Hernia surgeries
Cataract surgeries
•
Preoperative assessment
Perioperative management
Discharge
• Excision of lumps, excision of foreign body
• Parotidectomy
• Laparoscopic surgeries such as cholecystectomy
TYPES OF CARE
A.Office-based care: The investigations and ambula-
tory interventions are performed on an outpatient
basis, providing ready access to patients. The disadvantage is that vey few procedures performed
under local anaesthesia are included in this.
Procedures that need general anaesthesia are not
performed as this requires additional equipment and
healthcare personnel.
B. Stand-alone day care surgery: The surgeries in this
care are performed in an isolated facility, either on a
remote site or in the campus of a parent hospital.
Procedures are limited to those performed under local
anaesthesia, regional anaesthesia or minor procedures under general anaesthesia. This is to avoid
overnight admissions which need to be transferred
to the parent hospital, which may be some distance
away.
TYPE OF SURGERY FACILITIES
.Self-contained integrated day: These are well-
A
equipped hospitals having reception area, operation
theatres and postoperative ward. Many surgeries can
be performed here including laparoscopic cholecystectomies, laparoscopic hernia surgeries, etc.
There should be a good cooperation between all
persons involved in the day case surgery. Patients
should be able to understand the instructions given
47
48
Manipal Manual of Surgery
to him by the consultant. He should be able to come
back to the hospital in case of any complications.
B. Integrated day and short-stay surgery facilities:
Here day care and short-stay surgery are feasible,
where challenging procedures or day surgery on a
less fit patient can be considered.
SELECTION CRITERIA
A
. Medical Criteria
1. Age: Physiological health of the patients is more
important than the chronological age. There is no
upper age limit.
2. Comorbidity: American S
ociety of Anesthesiologists
(ASA) classification is traditionally used to evaluate
the patients (Table 13.1).
ASA 1 and 2 patients are confined to the stand-alone
units, whereas ASA 3 patients are suitable for
hospital-integrated units. Patients with hypertension
are considered for day surgery when blood pressure
is below 180/110 mmHg. Patients with significant
respiratory and cardiac disease have to be reviewed
by anaesthetist before being accepted for day surgery.
3. Obesity: Obesity is defined as body mass index of
2
more than 30 kg/m
. Traditionally, guidelines
towards obese patients were conservative due to the
fear of complications. The course of these patients is
uneventful, although there is increased risk for nonserious intraoperative and postoperative respiratory
complications. Complications of morbid obesity such
as sleep apnoea, hypertension and congestive cardiac
failure should be managed preoperatively with an
experienced team.
4. Epilepsy: Patients with controlled epilepsy on
medications should be managed as normal patients.
It is important not to omit the medications in the preoperative medications. Patients with poorly controlled
epilepsy on medications should be managed preoperatively with a medical team.
5. Diabetes: The incidence of diabetes is on the increas-
ing trend worldwide. An HbA1c of 8.5% indicates a
good control. Patients with well-controlled type 1
and 2 diabetes mellitus can be considered for day
surgery. The complications of diabetes such as renal
disease, cardiovascular disease should be evaluated
pre-operatively by an experienced team. These
patients should not be given oral hypoglycemic
agents. Also, they should be operated first rather than
late in the evening. If the patient is on afternoon or
evening lists or undergoing a complex surgery, he
can be managed with the help of a diabetic team or
the anaesthetist.
6. Anticoagulants: Preoperative risk assessment with
a cardiologist is important in managing patients on
anticoagulation when it is felt that surgery will
require its discontinuation. Patients are often on
anticoagulation due to atrial fibrillation, venous
thromboembolism, o
r a prosthetic heart valve.
Patients may be receiving anticoagulants following
stenting or coronary artery bypass graft. A few drugs
may have to be stopped for 7 days before surgery.
One such example is clopidogrel.
7. Smoking: Patient should stop smoking at least
48 hours before surgery. Substance abuse patients are
not the candidates for day case/care surgery.
B. Social Criteria
A patient accompanied by a responsible adult is the key
to a safe and comfortable discharge. A travel time of
less than one hour is considered ideal although the
comfort of the journey is more important. The means of
contacting the hospital, if a complication occurs, is an
important aspect of a safe discharge. As mentioned
earlier, due to these reasons, many of our patients will
not get the benefit of day case/surgery.
C. Surgical Criteria
An operating time of 2 hours in duration is considered
safe as a day surgery. Suitable control of pain and the
ability to eat and drink a reasonable amount is the main
requirement. Venous thromboembolism risk assessment
is important in patients undergoing complex surgery.
Table 13.1 The American Society of Anesthesiologists
(ASA) physical status classification
ASA 1 A normal healthy patient
ASA 2 A patient with mild systemic disease
ASA 3 A patient with severe systemic disease
ASA 4 A patient with severe systemic disease that is a
constant threat to life
ASA 5 A moribund patient who is not expected to survive
Section I • Basic Principles of Surgery
without the operation
PREOPERATIVE ASSESSMENT
The preoperative assessment of the patient is best done
by an anaesthetist who specializes in day surgery. It
should be done early in the pathway to allow time to
optimise health problems before surgery. All patients
should be considered for day surgery unless proven
otherwise. Relevant investigations are conducted to
assess the fitness of the patient for surgery. Informed
and written consent is taken after informing the patient
about admission, operation, and discharge.
Day Case/Care Surgery
49
PERIOPERATIVE MANAGEMENT
• Scheduling: Day surgeries are preferably planned in
the morning to make monitoring and early discharge
of the patient feasible. If there is a list in the afternoon,
local and regional anaesthesia cases are planned for
later in the day. Mixing of day case and complex
inpatient cases is not recommended.
• Anaesthesia and analgesia: Multimodal analgesia is
required to make a day case surgery successful. It is
started in the preoperative period with paracetamol
and non-steroidal anti-inflammatory drugs. Intraoperative anaesthesia is maintained by any of the
inhalational agents. The anaesthetist rather than the
drugs used matter more. Total intravenous anaesthesia
(TIVA) offers the advantage of reduced postoperative
nausea and vomiting. Short-acting agents are preferred whenever feasible. When morphine is used, it
is given in minimal doses to reduce postoperative
nausea and vomiting. Local anaesthetic such as
bupivacaine when injected into the wounds helps
prolong the effect of analgesia. Postoperative monitoring of pain is important and further doses of analgesia
should be given accordingly to make the patient
comfortable and fit for discharge on the same day.
• Postoperative complications: The complications of
day surgery are like that of inpatient surgery.
However, since day surgery patients are discharged
on the same day, monitoring in the immediate
postoperative period is important. Reactionary
hemorrhage is uncommon but important in cases
such as tonsillectomy and laparoscopic procedures.
Slow bleeding and hypovolaemia can be dangerous.
In India such surgeries can be done only if patient
understands the complications and also he has the
facility to call for ambulance and reach the hospital
quickly. Covert haemorrhage is a danger in laparoscopic procedures and it might manifest as delayed
recovery or uncontrollable abdominal pain. High
index of suspicion is required in such patients and
timely intervention is vital. Postoperative nausea and
vomiting is not uncommon and needs to be managed
to facilitate same day discharge.
DISCHARGE
Discharge criteria are important in assessing a patients
fitness for discharge which is done by a trained day
surgery nurse. Postoperative review by a surgeon is
important but the discharge should not be delayed by
failure of their timely attendance. There must be a caretaker person to look after the patient once he or she
gets discharged after the surgery. He should be able to
provide some simple basic care such as pain relief tablets
or even to dress a small ooze from the suture line. He
should available for the next 24 hours to the patient soon
after the surgery.
Discharge Criteria
1. Just before discharge, look at the operated sites.
Example: Hernial site at groin, oral cavity as in
tonsillectomy. If any degree of suspicion arises,
observe them more carefully for another few hours.
If any oozing or bleeders are identified within
6–8 hours means better to stop the bleeding and delay
discharge.
. Look at the vitals: Pulse rate, breathing, blood
2
pressure. Only when they are stable, discharge can
be considered.
3. Talk to the patient and ask him to obey a few
commands such as showing the tongue, identifying
relatives or hospital. Simple leading question is—
where are you now? Do you have any pain? Can you
tolerate this pain?
4. A few common side effects of anaesthetics such as
nausea or vomiting are present or not, if present
should be minimal. Such patient tolerates liquid and
semi-solid food.
5. A contact number should be given to the patient in
case of any emergency.
REFERENCES
1. Bailey and Love’s short practise of surgery, 27th edition.
2. McWhinnie D, Jackson I, Smith I, Skues M. Patient safety in the
ambulatory pathway. British Association of Day Surgery Handbook
Series. London: BADS, 2013.
Section I • Basic Principles of Surgery
14
Principles of Safe General Surgery
Introduction
WHO surgical safety checklist (2008)
SU11.6: Describe principles of safe general surgery.
INTRODUCTION
Since the last three decades, tremendous growth has
been seen in a number of surgeries performed. World
has also seen advances in all medical fields including
surgery. Minimal access surgery is one of the major
changes which happened in these 30 years and has been
accepted very well by surgeons and patients. In fact,
surgeon’s aim is not only to operate but also operate
with minimal morbidity and least mortality. Minimal
access surgery or laparoscopic surgery is one example
of such developments. It is also important that many
such skilled surgeries require training. In a few cases,
learning curve is long. An attempt to do surgery may
land with complications, compromising patient’s safety.
Legal issues are also becoming more common in the last
3 decades. Thus, safe practise of general surgery aims
to achieve maximum success. It will also decrease litigations for surgeons. Let us look at those principles.
WHO SURGICAL SAFETY CHECKLIST (2008)
World Health Organisation (WHO) in 2008 released a
checklist consisting of 19 items. If one follows this
system, one can decrease number of deaths/blunders/
complications related to surgery. Worldwide a large
number of deaths or errors occur in the operating table
which results in mortality. It is a simple checklist to
implement. Many centres in the world have used this
and have reduced the complications related to
instruments or adverse events which occur in the
hospital before or during or after conduct of a surgical
Five steps to safer surgery
procedure. Dr Makary, Professor of Surgery, Johns
Hopkins University School of Medicine, is the creator
of The Surgery Checklist (Fig. 14.1).
Surgery is basically a teamwork. If the entire team
consisting of surgeon, anaesthetist and nursing staff
know about the patient disease, problems, if any,
including allergy, indication for surgery, possible
complications and recovery in the postoperative period,
many of the complications could have been avoided.
Every surgery has a critical event. Before proceeding,
the surgeon can discuss this with his colleagues/other
surgeons and go ahead. Classical example: Before ligation
and division of cystic duct in cases of difficult cholecystectomy. A wrong decision at this stage can have
serious consequences of division of CBD and associated
with serious complications and mortality also.
In Western countries, the consultant who examines
the patient may not be the operating surgeon. Often
appointments are given and patient comes to the
hospital on the day of surgery. Surgeon comes to OT,
he will see a few CT scans or reports and operate. He
might have been busy also. Because of this, wrong side
of the patient has been operated many a time. Wrong
side breast lump has been removed. Due to communication errors between nursing staff and surgeons, nurses
may not be well prepared for an unexpected emergency
which necessitates additional set of instruments, e.g.
vascular injury. If a prior intimation is given to them,
such situations can be avoided. This can happen
anywhere and hence, WHO advises the use of checklist.
Sign in means checking before induction of
anaesthesia, time out means before skin incision and
sign out means before the patient leaves the operating
room. These principles help in avoiding operating on
50
Principles of Safe General Surgery
51
Fig. 14.1: Surgical safety checklist (Reproduced with permission of the World Health Organization, wholibdoc.who.int/publications/
2009/9789241598590_eng_ Checklist.pdf”)
wrong patients, wrong side, wrong procedure.
Anticipating major events such as vascular injuries or
excessive bleeding, etc. are also part of the checklist. It
also helps in better coordination between operating
surgeons, anaesthetists, and nurses. Simple checklists
will avoid such gross blunders or errors. Counting mops
and needles are also part of this. The list can be modified
depending upon the local hospital policies and practises.
Modification of this checklist, a single 5-step approach,
advocated by the National Patient Safety Agency
(NPSA) for all patients in England and Wales undergoing surgical procedures is given below.
Five Steps to Safer Surgery
A simple 5-step approach, “Five Steps to Safer Surgery”
is a surgical safety checklist. It involves briefing,
sign-in, timeout, sign-out and debriefing.
1. Briefing: Before the procedure starts. A briefing
about the patient, what is the disease, who is doing
the surgery, who are assisting, what is the plan and
what are the possible complications, is there possibility of excessive blood loss. Please note safety list is
not about discussing complications of surgery with
the patient but briefing to the team. One example is
surgery team is informed in advance to ensure their
availability.
2. Sign in: Before induction of anaesthesia, reconfirm
whether consent is taken or not, presence of allergy,
anticipated blood loss, anaesthesia machine and
drugs. Check the side of marking specially when
lesions are small—breast lumps, lymph nodes.
3. Time out: Stop for a moment before starting incision.
Again, confirm patient identity, surgical site infection
bundle, thromboprophylaxis, antibiotics or any
adverse events which can happen—may be all these
are already discussed but check again.
4. Sign out: At the end of the procedure, check sponge
count, needle and sharp count, check position of tubes
and tourniquets. Discuss possible complications with
doctors as well as nurses in the team.
5. Debriefing: At the end of the procedure, discuss
again about what has been done and what should
not have been done. Example: Why did I injure
internal jugular vein in thyroidectomy? Why did the
creation of pneumoperitoneum take a long time? Was
there any instrument failure? Should anything else
be improved? This is done with a view to improve
care of patients in the future.
carcinoma parotid with doubtful infiltration of facial
nerve. Here a nurse is requested to keep nerve
stimulator ready, anaesthesia consultant is informed
that muscle relaxants must be avoided
and a plastic
REFERENCE
Ann R Coll Surg Engl. 2011 Oct; 93(7): 501–503.
Section I • Basic Principles of Surgery
15
Metabolic Response to Injury
Energy expenditure
Changes in skeletal muscle
Changes in liver protein metabolism
SU1.1: Describe basic concepts of homeostasis. Enumerate the
metabolic changes in injury and their mediators.
‘Homeostasis’ is a state of dynamic equilibrium, wherein
the body maintains its key physiological variables
within a predefined range through feedback mechanisms. As opposed to its literal meaning suggestive of
‘stagnancy’, homeostasis allows a wide range of
continuous changes of body parameters within their
physiological limits, letting various compensatory
mechanisms to act in case of any deviation from
normalcy. Sir David Cuthbertson (1942) proposed that
human beings respond to injuries in two distinct phases
of hypermetabolic state, namely the ‘ebb phase’ and the
‘flow phase’. The ‘ebb phase’ begins immediately
following an event of stress such as burns, trauma,
surgery or critical illness and lasts for 24–48 hours.
Generally, hemodynamic disturbances like hypotension
is seen in this phase, hence it aims to conserve circulating
fluid volume and energy, and is characterised by
reductions in basal metabolic rate (BMR), cardiac
output, oxygen consumption; lactic acidosis and glucose
intolerance. The renin–angiotensin cascade is an
important component of the ‘ebb phase’. The hormones
responsible are the adrenal hormones (i.e. catecholamines, cortisol and aldosterone). The ‘flow phase’
follows the ‘ebb phase,’ lasts for days to weeks
depending on the severity of injury and is concerned
with recovery and repair following the initial injury. It
is a catabolic (breakdown) phase that prevents further
tissue damage and protects critical organ function. The
catecholamines (adrenaline) are mainly responsible for
Response to injury
– Neuroendocrine response
– Immune response
the increased energy production and consumption. This
is followed by an anabolic (synthetic) phase, the onset
of which is again based on the injury severity. The transition happens about 3–8 days after an uncomplicated
elective surgery but may take several weeks after sepsis
or severe trauma. Clinically it coincides with the oral
intake of fluids, soft diet and diuresis and may last for
several months, during which it replaces body protein
and fat stores, normalizing the positive nitrogen balance
after the metabolic response to stress is stopped. The
following issues are important aspects of the metabolic
response to stress.
ENERGY EXPENDITURE
During stress, energy expenditure increases by 15–25%
due to:
• Central thermodysregulation caused by pro-
inflammatory cytokines.
• Increased sympathetic activity.
• Increased lactate production in ischaemic areas which
in turn gets metabolised by the energy consuming
Cori cycle.
• Increased cardiac output.
• Increased protein turnover.
The clinical importance is the awareness of increase
in this energy expenditure in order to determine
metabolic and nutritional support for the patient.
CHANGES IN SKELETAL MUSCLE
During the catabolic phase of stress response, increased
protein turnover is seen. There is muscle wasting due to:
52
Metabolic Response to Injury
53
• Increased muscle protein degradation
• Decreased muscle protein synthesis.
This results in the release of amino acids, mainly
alanine and glutamine, which are used by the liver and
immune system for the synthesis of proteins, such as
acute phase proteins and cytokines. Although all types
of muscles contain proteins, proteins from skeletal
and smooth muscles (in that order) are preferentially
catabolised compared to those from cardiac muscles.
The main pathways which govern protein catabolism
in skeletal muscles are:
• ATP-dependent ubiquitin proteasome pathway
• Lysosomal cathepsin
• Calcium calpain pathway
However, in the critically ill, the amino acids released
by protein catabolism in muscle cannot be used for
protein resynthesis. A negative nitrogen balance occurs
and if adequate nutritional support is not provided,
rapid loss of muscle tissue occurs resulting in dependence on mechanical ventilation and inadequate
healing. Hence, exaggerated skeletal muscle catabolism
results in asthenia, increased fatigability, poor quality
of life, and increased morbidity and mortality. Another
physiological defect in such conditions is impaired
excitation–contraction coupling at the level of the
sarcolemma and sarcoplasmic reticulum. This condition
has been termed ‘critical illness myopathy.’
CHANGES IN LIVER PROTEIN METABOLISM
Normally, the liver synthesises two types of proteins:
. Structural proteins
1
2. Export proteins, e.g. albumin.
Based on response to stress, the proteins synthesised
by liver can be divided into:
1. Positive acute phase reactants, e.g. fibrinogen,
C-reactive proteins (CRP) and ceruloplasmin
2. Negative acute phase reactants, e.g. albumin.
As the name suggests, they increase and decrease
respectively in response to stress.
Clinical significance: In response to IL-6, ‘acute phase
response’ occurs which is characterized by production
of acute phase proteins by the liver that act as inflammatory mediators, anti-proteinases and scavengers in tissue
repairs. In this phase, there is granulocytosis, increase
in serum concentrations of CRP and ceruloplasmin,
decrease in serum concentrations of albumin and
transferrin, changes in serum concentrations of divalent
cations (copper increases; zinc and iron decrease).
Hence, investigating for these laboratory parameters
might suggest an underlying inflammatory process,
especially when anticipated after an event of stress.
.
Special note on albumin: Albumin is the major protein
synthesised by liver. Hypoalbuminemia is commonly
associated with malnutrition and severe stress/sepsis.
It is tempting to presume that a fall in albumin level
during stress is due to diversion of its synthesis by the
liver towards synthesis of positive acute phase reactants
instead. This might not be true. The serum level of
albumin is governed by its rates of synthesis and
transcapillary escape. During stress, the transcapillary
escape rate of albumin increases about 3 times. This is
because of increased microvascular permeability, which
results in hypoalbuminemia during stress/sepsis.
Insulin resistance: After an event of stress, like a
major surgery, stress hormones including glucagon,
catecholamines, growth hormone and cortisol are
secreted and inflammatory reaction is generated by
cytokines all of which enhance the action of insulin, due
to which amino acids, free fatty acids and glucose are
released into the bloodstream from various tissues. The
body also switches from glucose to fat for substrate
metabolism. This results in stress-hyperglycemia and
an insulin resistant state, particularly in critically ill
patients with sepsis. One of the clinical implications here
is to infuse insulin to normalize the glucose level and
good glycemic control will improve the outcome of
critically ill patients.
RESPONSE TO INJURY
Introduction
The ultimate aim of the response of the body to injury
is to maintain the ‘milieu interieur’—a stable internal
environment that allows biological processes to proceed
despite varying external environmental conditions. It
depends upon the severity of the injury and can be
considered under the following headings:
• Neuroendocrine response
• Immunological response
• Metabolic response
Neuroendocrine Response (Fig. 15.1)
One of the earliest pathways to get activated following
injury is the ‘neuroendocrine pathway’. The neuroendocrine pathway starts with nociceptive receptors
and involves the spinal cord, thalamus, hypothalamus,
and pituitary. Stimulation of the hypothalamus is a key
event in the pathway and results in:
• Release of corticotrophin-releasing hormone (CRH),
which triggers the release of ACTH from the anterior
pituitary. ACTH acts on the adrenals to increase the
secretion of cortisol and aldosterone.
TSH, FSH, LH may increase or decrease.
The levels of
Section I • Basic Principles of Surgery