General anaesthesia
Definition
General anaesthesia (or general anesthesia) is a
state of unconsciousness and loss of protective reflexes
resulting from the administration of one or more general
anaesthetic agents. A variety of medications may be
administered, with the overall aim of ensuring hypnosis,
amnesia, analgesia, relaxation of skeletal muscles, and loss
of control of reflexes of the autonomic nervous system.
The optimal combination of these agents for any given
patient and procedure is typically selected by an
anaesthesiologist or another provider such as a nurse
anaesthetist, in consultation with the patient and the
medical or dental practitioner who is performing the
operative procedure.
Biochemical
mechanism of action
The biochemical mechanism of action of general
anaesthetics is not yet well understood. To induce
unconsciousness, anaesthetics affect the GABA and NMDA
systems. For example, halothane is a GABA agonist and
ketamine is an NMDA receptor antagonist
Preanaesthetic evaluation
Prior to planned operation or procedure, the anaesthetist
reviews the medical record and/or interviews the patient
to determine the best combination of drugs and dosages
and the degree to which monitoring will be required to
ensure a safe and effective procedure. Key factors of this
evaluation are the patient's age, body mass index,
medical and surgical history, current medications,
and fasting time. Thorough and accurate answering of
the questions is important so that the anaesthetist can
select the proper anaesthetic drugs and procedures. For
example, a patient who consumes significant quantities of
alcohol or illicit drugs could be undermedicated if s/he
fails to disclose this fact. This in turn could then lead to
anaesthesia awareness or dangerously high blood
pressureCommonly used medications (e.g., sildenafil) can
interact with anaesthesia drugs; failure to disclose such
usage can also increase the risk to the patient
An important aspect of the preanaesthetic evaluation is
that of the patient's airway, involving inspection of the
mouth opening and visualisation of the soft tissues of the
pharynx. The condition of teeth and location of dental
crowns and caps are checked, neck flexibility and head
extension observed. If a tracheal tube is indicated and
airway management is deemed difficult, then alternative
methods of tracheal intubation, such as fibreoptic
intubation, may be required as part of the anaesthetic
management.
Premedication
Anaesthesiologists may prescribe or administer a
premedication prior to administration of a general
anaesthetic. Anaesthetic premedication consists of a drug
or combination of drugs that serve to complement or
otherwise improve the quality of the anaesthetic.
One example of this is the preoperative administration of
clonidine, an alpha-2 adrenergic agonist. Clonidine
premedication reduces the need for anaesthetic induction
agents, as well as the need for volatile anaesthetic agents
during maintenance of general anaesthesiaand the need
for postoperative analgesicsClonidine premedication also
reduces postoperative shivering, postoperative nausea and
vomiting and emergence deliriumIn children, clonidine
premedication is at least as effective as benzodiazepines,
in addition to having a more favourable side effect profileIt
also reduces the incidence of post-operative delirium
associated with sevoflurane anaesthesiaAs a result
clonidine has become a popular agent for anaesthetic
premedication Drawbacks of oral clonidine include the
fact that it can take up to 45 minutes to take full effect
hypotension and bradycardia
Midazolam, a benzodiazepine characterized by a rapid
onset and short duration relative to other
benzodiazepines, is effective in reducing preoperative
anxiety, including separation anxiety associated with
separation of children from their parents and induction of
anaesthesia Dexmedetomidine and certain atypical
antipsychotic agents are other drugs which are used
particularly in very uncooperative children.
Melatonin has been found to be effective as an anaesthetic
premedication in both adults and children due to its
hypnotic, anxiolytic, sedative, antinociceptive and
anticonvulsant properties. Unlike midazolam, melatonin
does not impair psychomotor skills or adversely effect the
quality of recovery. Recovery is more rapid after melatonin
premedication than with midazolam, and there is also a
reduced incidence of post-operative agitation and
delirium. Melatonin premedication also reduces the
required induction dose of propofol and thiopental.
Another example of anaesthetic premedication is the
preoperative administration of beta adrenergic antagonists
to reduce the incidence of postoperative hypertension,
cardiac dysrhythmia or myocardial infarctionOne may
choose to administer an antiemetic agent such as
droperidol or dexamethasone to reduce the incidence of
postoperative nausea and vomitingor subcutaneous
heparin or enoxaparin to reduce the incidence of deep vein
thrombosis Other commonly used premedication agents
include opioids such as fentanyl or sufentanil,
gastrokinetic agents such as metoclopramide, and
histamine antagonists such as famotidine.
Non-pharmacologic preanaesthetic interventions include
playing relaxing music, massage, and reducing ambient
light and noise levels in order to maintain the sleep-wake
cycle. These techniques are particularly useful for
paediatric and mentally retarded patients. Other options
for children who refuse or cannot tolerate pharmacologic
premedication include interventions by clowns and child
life specialists. Minimizing sensory stimulation or
distraction by video games may also help to reduce anxiety
prior to or during induction of general anaesthesia
Stages of anaesthesia
The four stages of anaesthesia were described in 1937.
Despite newer anaesthetic agents and delivery techniques,
which have led to more rapid onset and recovery from
anaesthesia, with greater safety margins, the principles
remain.



Stage 1: Stage 1 anaesthesia, also known as the
"induction", is the period between the initial
administration of the induction agents and loss of
consciousness. During this stage, the patient
progresses from analgesia without amnesia to
analgesia with amnesia. Patients can carry on a
conversation at this time.
Stage 2: Stage 2 anaesthesia, also known as the
"excitement stage", is the period following loss of
consciousness and marked by excited and delirious
activity. During this stage, respirations and heart rate
may become irregular. In addition, there may be
uncontrolled movements, vomiting, breath holding,
and pupillary dilation. Since the combination of
spastic movements, vomiting, and irregular
respirations may lead to airway compromise, rapidly
acting drugs are used to minimize time in this stage
and reach stage 3 as fast as possible.
Stage 3: Stage 3, "surgical anaesthesia". During this
stage, the skeletal muscles relax, and the patient's
breathing becomes regular. Eye movements slow,
then stop, and surgery can begin. It has been divided
into 4 planes:
1. eyes initially rolling, then becoming fixed
2. loss of corneal and laryngeal reflexes
3. pupils dilate and loss of light reflex
4. intercostal paralysis, shallow abdominal respiration,
dilated pupils

Stage 4: Stage 4 anaesthesia, also known as
"overdose", is the stage where too much medication
has been given relative to the amount of surgical
stimulation and the patient has severe brain stem or
medullary depression. This results in a cessation of
respiration and potential cardiovascular collapse.
This stage is lethal without cardiovascular and
respiratory support. This can be fatal.
Induction
Induction of general anaesthesia is usually conducted in a
medical facility, most commonly in an operating room.
However, general anaesthesia may also be conducted in
many other locations, such as an endoscopy suite,
radiology or cardiology department, emergency
department, ambulance, or at the site of a disaster where
extrication of the patient may be impossible or
impractical.
Anaesthetic agents may be administered by various routes,
including inhalation, injection (intravenous,
intramuscular or subcutaneous), oral, and rectal. After
administration by one or more of these routes, the agents
gain access to the blood. Once in the circulatory system,
they are transported to their biochemical sites of action in
the central and autonomic nervous systems, where they
exert their pharmacologic effects.
Most general anaesthetics today are induced either by
intravenous injection or breathing a volatile anaesthetic
through an anaesthetic circuit (inhalational induction).
Onset of anaesthesia is faster with intravenous injection
than with inhalation, taking about 10–20 seconds to
induce total unconsciousness.[ This has the advantage of
avoiding the excitatory phase of anaesthesia (see below),
and thus reduces complications related to induction of
anaesthesiaCommonly used intravenous induction agents
include propofol, sodium thiopental, etomidate, and
ketamine. An inhalational induction may be chosen by the
anaesthesiologist where intravenous access is difficult to
obtain, where difficulty maintaining the airway is
anticipated, or due to patient preference (e.g. children).
Sevoflurane is currently the most commonly used agent
for inhalational induction, because it is less irritating to
the tracheobronchial tree than other volatile anaesthetic
agents
Physiologic monitoring
Monitoring involves the use of several technologies to
allow for a controlled induction of, maintenance of and
emergence from general anaesthesia.
1. Continuous Electrocardiography (ECG): The
placement of electrodes which monitor heart rate and
rhythm. This may also help the anaesthetist to
identify early signs of heart ischaemia.
2. Continuous pulse oximetry (SpO2): The placement of
this device (usually on one of the fingers) allows for
early detection of a fall in a patient's haemoglobin
saturation with oxygen (hypoxaemia).
3. Blood Pressure Monitoring (NIBP or IBP): There are
two methods of measuring the patient's blood
pressure. The first, and most common, is called noninvasive blood pressure (NIBP) monitoring. This
involves placing a blood pressure cuff around the
patient's arm, forearm or leg. A blood pressure
machine takes blood pressure readings at regular,
preset intervals throughout the surgery. The second
method is called invasive blood pressure (IBP)
monitoring. This method is reserved for patients with
significant heart or lung disease, the critically ill,
major surgery such as cardiac or transplant surgery,
or when large blood losses are expected. The invasive
blood pressure monitoring technique involves placing
a special type of plastic cannula in the patient's artery
- usually at the wrist or in the groin.
4. Agent concentration measurement - Common
anaesthetic machines have meters to measure the
percent of inhalational anaesthetic agent used (e.g.
sevoflurane, isoflurane, desflurane, halothane etc.).
5. Low oxygen alarm - Almost all circuits have a backup
alarm in case the oxygen delivery to the patient
becomes compromised. This warns if the fraction of
inspired oxygen drops lower than room air (21%) and
allows the anaesthetist to take immediate remedial
action.
6. Circuit disconnect alarm - indicates failure of circuit
to achieve a given pressure during mechanical
ventilation.
7. Carbon dioxide measurement (capnography)measures the amount of carbon dioxide expired by
the patient's lungs. It allows the anaesthetist to assess
the adequacy of ventilation
8. Temperature measurement to discern hypothermia
or fever, and to aid early detection of malignant
hyperthermia.
9. EEG or other system to verify depth of anaesthesia
may also be used. This reduces the likelihood that a
patient will be mentally awake, although unable to
move because of the paralytic agents. It also reduces
the likelihood of a patient receiving significantly
more amnesic drugs than actually necessary to do the
job.
Airway management
With the loss of consciousness caused by general
anaesthesia, there is loss of protective airway reflexes
(such as coughing), loss of airway patency and sometimes
loss of a regular breathing pattern due to the effect of
anaesthetics, opioids, or muscle relaxants. To maintain an
open airway and regulate breathing within acceptable
parameters, some form of "breathing tube" is inserted in
the airway after the patient is unconscious. To enable
mechanical ventilation, an endotracheal tube is often used
(intubation), although there are alternative devices such as
face masks or laryngeal mask airways.
Neuromuscular blockade
"Paralysis" or temporary muscle relaxation with a
neuromuscular blocker is an integral part of modern
anaesthesia. The first drug used for this purpose was
curare, introduced in the 1940s, which has now been
superseded by drugs with fewer side effects and generally
shorter duration of action. Muscle relaxation allows
surgery within major body cavities, e.g. abdomen and
thorax without the need for very deep anaesthesia, and is
also used to facilitate endotracheal intubation.
Acetylcholine, the natural neurotransmitter substance at
the neuromuscular junction, causes muscles to contract
when it is released from nerve endings. Muscle relaxants
work by preventing acetylcholine from attaching to its
receptor. Paralysis of the muscles of respiration, i.e. the
diaphragm and intercostal muscles of the chest requires
that some form of artificial respiration be implemented. As
the muscles of the larynx are also paralysed, the airway
usually needs to be protected by means of an endotracheal
tube. Monitoring of paralysis is most easily provided by
means of a peripheral nerve stimulator. This device
intermittently sends short electrical pulses through the
skin over a peripheral nerve while the contraction of a
muscle supplied by that nerve is observed. The effects of
muscle relaxants are commonly reversed at the
termination of surgery by anticholinesterase drugs.
Examples of skeletal muscle relaxants in use today are
pancuronium, rocuronium, vecuronium, atracurium,
mivacurium, and succinylcholine.
Maintenance
The duration of action of intravenous induction agents is
generally 5 to 10 minutes, after which time spontaneous
recovery of consciousness will occur. In order to prolong
anaesthesia for the required duration (usually the duration
of surgery), anaesthesia must be maintained. Usually this
is achieved by allowing the patient to breathe a carefully
controlled mixture of oxygen, nitrous oxide, and a volatile
anaesthetic agent or by having a carefully controlled
infusion of medication, usually propofol, through an
intravenous catheter. The inhalation agents are
transferred to the patient's brain via the lungs and the
bloodstream, and the patient remains unconscious.
Inhaled agents are frequently supplemented by
intravenous anaesthetics, such as opioids (usually fentanyl
or a fentanyl derivative) and sedative-hypnotics (usually
propofol or midazolam). Though for a propofol-based
anaesthetic, supplementation by inhalation agents is not
required. At the end of surgery the volatile or intravenous
anaesthetic is discontinued. Recovery of consciousness
occurs when the concentration of anaesthetic in the brain
drops below a certain level (usually within 1 to 30 minutes
depending upon the duration of surgery). In the 1990s a
novel method of maintaining anaesthesia was developed in
Glasgow, UK. Called TCI (target controlled infusion), this
involves using a computer controlled syringe driver
(pump) to infuse propofol throughout the duration of
surgery, removing the need for a volatile anaesthetic, and
allowing pharmacologic principles to more precisely guide
amount of infusion of the drug. Purported advantages
include faster recovery from anaesthesia, reduced
incidence of post-operative nausea and vomiting, and
absence of a trigger for malignant hyperthermia. At
present, TCI is not permitted in the United States] Other
medications will occasionally be given to anaesthetized
patients to treat side effects or prevent complications.
These medications include antihypertensives to treat high
blood pressure, drugs like ephedrine and phenylephrine to
treat low blood pressure, drugs like albuterol to treat
asthma or laryngospasm/bronchospasm, and drugs like
epinephrine or diphenhydramine to treat allergic
reactions. Sometimes glucocorticoids or antibiotics are
given to prevent inflammation and infection, respectively.
Postoperative care
The anaesthesia should conclude with a pain-free
awakening and a management plan for postoperative pain
relief. This may be in the form of regional analgesia, oral,
transdermal or parenteral medication. Minor surgical
procedures are amenable to oral pain relief medications
such as paracetamol and NSAIDs such as ibuprofen.
Moderate levels of pain require the addition of mild
opiates such as tramadol. Major surgical procedures may
require a combination of modalities to confer adequate
pain relief. Parenteral methods include patient-controlled
analgesia (PCA) involving a strong opiate such as
morphine, fentanyl or oxycodone. Here, to activate a
syringe device, the patient presses a button and receives a
preset dose or "bolus" of the drug (e.g. one milligram of
morphine). The PCA device then "locks out" for a preset
period, e.g. 5 minutes, to allow the drug to take effect. If
the patient becomes too sleepy or sedated, they make no
more morphine requests. This confers a fail safe aspect
which is lacking in continuous opiate infusion techniques.
Shivering is a frequent occurrence in the post-operative
period. Apart from causing discomfort and exacerbating
post-operative pain, shivering has been shown to increase
oxygen consumption, catecholamine release, cardiac
output, heart rate, blood pressure and intra-ocular
pressure. There are a number of techniques used to reduce
this occurrence, such as increasing the ambient
temperature in theatre, using conventional or forced warm
air blankets and using warmed intravenous fluids
Perioperative mortality
Main article: Perioperative mortality
Most perioperative mortality is attributable to
complications from the operation (such as haemorrhage,
sepsis, and failure of vital organs) or pre-existing medical
conditionsMost current estimates of perioperative
mortality range from 1 death in 53 anaesthetics to 1 in
5,417 anaesthetics. However, a 1997 Canadian
retrospective review of 2,830,000 oral surgical procedures
in Ontario between 1973–1995 reported only four deaths
in cases in which either an oral and maxillofacial surgeon
or a dentist with specialized training in anaesthesia
administered the general anaesthetic or deep sedation.
The authors calculated an overall mortality rate of 1.4 per
1,000,000 The largest and most recent study of
postoperative mortality was published in 2010. In this
review of 3.7 million elective open surgical procedures
performed on inpatients at 102 hospitals in the
Netherlands during 1991–2005, postoperative mortality
from all causes was observed in 67,879 patients, for an
overall rate of 1.85%.The wide disparity between the
results of these studies may be the result of differences in
operational definitions and reporting sources.
Mortality directly related to anaesthetic management is
significantly less common, and may include such causes as
pulmonary aspiration of gastric contents, asphyxiation[18]
and anaphylaxis. These in turn may result from
malfunction of anaesthesia-related equipment or more
commonly, human error. A 1978 study found that 82% of
preventable anaesthesia mishaps were the result of human
error. In a 1954 review of 599,548 surgical procedures at
10 hospitals in the United States between 1948–1952, 384
deaths were attributed to anaesthesia, for an overall
mortality rate of 0.64%. In 1984, after a television
programme highlighting anaesthesia mishaps aired in the
United States, American anaesthesiologist Ellison C.
Pierce appointed a committee called the Anesthesia
Patient Safety and Risk Management Committee of the
American Society of Anesthesiologists. This committee
was tasked with determining and reducing the causes of
peri-anaesthetic morbidity and mortality. An outgrowth of
this committee, the Anesthesia Patient Safety Foundation
was created in 1985 as an independent, nonprofit
corporation with the vision that "that no patient shall be
harmed by anesthesia". As with perioperative mortality
rates in general, the current mortality attributable to the
management of general anaesthesia is controversial The
incidence of perioperative mortality that is directly
attributable to anaesthesia ranges from 1 in 6,795 to 1 in
200,200 anaesthetics.
References
1. ^ Li X, Pearce RA (2000). "Effects of halothane on GABA(A) receptor kinetics:
evidence for slowed agonist unbinding". J. Neurosci. 20 (3): 899–907.
PMID 10648694.
2. ^ Harrison N, Simmonds M (1985). "Quantitative studies on some antagonists of
N-methyl D-aspartate in slices of rat cerebral cortex". Br J Pharmacol 84 (2):
381–91. PMID 2858237.
3. ^ Bergendahl, H; Lönnqvist, PA; Eksborg, S (Feb 2006). "Clonidine in paediatric
anaesthesia: review of the literature and comparison with benzodiazepines for
anesthetic premedication". Acta Anaesthesiol Scand 50 (2): 135–43.
doi:10.1111/j.1399-6576.2006.00940.x. PMID 16430532.
http://www3.interscience.wiley.com/cgi-bin/fulltext/118557949/HTMLSTART.
Retrieved 09-08-2010.
4. ^ Dahmani, S; Brasher, C; Stany, I; Golmard, J; Skhiri, A; Bruneau, B; Nivoche,
Y; Constant, I et al. (Jan 2010). "Premedication with clonidine is superior to
benzodiazepines. A meta analysis of published studies". Acta Anaesthesiol Scand
54 (4): 397–402. doi:10.1111/j.1399-6576.2009.02207.x. PMID 20085541.
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-6576.2009.02207.x/pdf.
Retrieved 09-08-2010.
5. ^ Rosenbaum, A; Kain, ZN; Larsson, P; Lönnqvist, PA; Wolf, AR (Sep 2009).
"The place of premedication in pediatric practice". Paediatr Anaesth 19 (9): 817–
28. doi:10.1111/j.1460-9592.2009.03114.x. PMID 19691689.
http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9592.2009.03114.x/pdf.
Retrieved 09-08-2010.
6. ^ Cox, RG; Nemish, U; Ewen, A; Crowe, MJ (Dec 2006). "Evidence-based clinical
update: does premedication with oral midazolam lead to improved behavioural
outcomes in children?". Can J Anaesth 53 (12): 1213–9.
doi:10.1007/BF03021583. PMID 17142656.
http://www.springerlink.com/content/8n317wx4w0136x35/fulltext.pdf.
Retrieved 09-08-2010.
7. ^ Bozkurt, P (Jun 2007). "Premedication of the pediatric patient - anesthesia for
the uncooperative child". Curr Opin Anaesthesiol 20 (3): 211–5.
doi:10.1097/ACO.0b013e328105e0dd. PMID 17479023.
http://journals.lww.com/coanesthesiology/Abstract/2007/06000/Premedication_of_the_pediatric_patient
__.11.aspx. Retrieved 09-08-2010.
Different Stages of Anesthesia:
Stage
Duration
Physical Signs
Onset
Giving Anesthesia to
loss of consciousness
Physical Signs
Excitement
From loss of
consciousness to loss of
eyelid reflexes
Irregular Heart beats
and Breathing
Surgical
Anesthesia
Loss of eyelid reflexes
to depression of vital
functions
Total Unconsciousness
Recovery or
Danger
Respiratory and
circulatory failure
No breathing and
heart beat