The secretion of the pituitary hormones antidiuretic hormone (ADH), adrenocorticotrophin (ACTH) and growth hormone (GH) is increased. ADH causes salt and water retention and also has vasopressor activity. ACTH leads to increased secretion of adrenal corticosteroids, cortisol and aldosterone, which further lead to salt and water retention. Growth hormone has a hyperglycaemic effect, but this effect is variable.

There is a generalized increase in sympathetic activity and the adrenal secretion of catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) is increased. These have predictable cardiovascular effects. Adrenaline also has metabolic effects, most notably hyperglycaemia. Increased production of renin from the kidney leads to activation of the renin–angiotensin–aldosterone pathway. Angiotensin II is a potent vasoconstrictor that increases blood pressure, while aldosterone increases renal salt and water retention.

The primary metabolic effects of the stress response are those of salt and water retention and increased catabolism. Salt and water retention is multifactorial in origin. The degree of water retention may exceed that of sodium retention, such that hyponatraemia is common.

The catabolic effects of catecholamines, steroids and growth hormone include increased glycogenolysis and gluconeogenesis, resulting in hyperglycaemia. Endogenous insulin production is increased in response, but an insulin infusion is often required to control the blood sugar. Fat and protein are broken down to provide energy substrates for tissue repair.

The stress response has evolved to provide survival advantages following severe injury or during critical illness. There is evidence that those that fail to mount an appropriate physiological response to critical illness have a poor outcome despite maximal support (e.g. elderly patients following trauma, burns or apparently minor head injury). At times, however, the stress responses can be detrimental. For example, exaggerated cardiovascular responses can lead to myocardial ischaemia and impaired tissue perfusion. Increased salt and water retention can lead to oliguria. Extreme catabolic responses can lead to severe wasting. For these reasons, there has been a great deal of interest in attempting to reduce the stress response.

The most important factors in reducing the stress response are ensuring good quality anaesthesia and peri-operative care, where possible preventing or minimizing tissue injury (e.g. laparoscopic surgery), careful fluid resuscitation, and good postoperative pain relief. (See Postoperative analgesia below.)

These techniques are extensively used to provide analgesia particularly in postoperative patients. Typically the patient will be established on such a device prior to transfer to a general ward. Although not intended for operation by nurses, they have been used safely and conveniently in this way in an ICU setting.

Care should be taken in setting devices up; a dedicated intravenous catheter or non-return valve should be used. There have been a number of problems due to excessive background dosing, surges of morphine on unblocking i.v. lines, and siphoning of contents under gravity from syringes. Avoid background infusions if possible. Position syringe drivers below the level of the patient to avoid siphoning, and use antireflux valves on giving sets. A typical PCAS regimen is shown in Box 14.1.

An increasing number of patients undergoing major surgery have analgesia provided by the epidural and spinal route. These techniques may also be used to relieve pain from trauma (e.g. fractured ribs) and ischaemic limbs.

Potential advantages include the avoidance of centrally acting sedative analgesic drugs, resulting in a more awake, cooperative and pain-free patient, who is better able to cough and clear airway secretions. In addition, in patients with ischaemic limbs, neuroaxial blockade (which includes sympathetic blockade) may provide both analgesia and improvement in perfusion of the ischaemic limb.

Detailed description of epidural techniques is beyond the scope of this book. When a patient is admitted with an epidural catheter in situ, you should make sure that you confirm the analgesic regimen with the responsible anaesthetist. Local anaesthetic and opioid drugs may be used alone or in combination. If opioid drugs are administered, additional systemic opioids should be administered with care because of the risk of respiratory depression. Typical regimens are shown in Table 14.1.

TABLE 14.1 Typical postoperative epidural infusion regimens

If breakthrough pain occurs and the patient is otherwise stable, give a 5–10 mL bolus of the epidural solution and then increase the infusion rate. This is normally effective within 10–15 min. Beware of hypotension.

The potential complications of epidural blockade are shown in Box 14.2.

Hypotension usually responds to fluid loading (500 mL colloid) and reducing the rate of epidural infusion. If significant hypotension develops, reduce or stop infusion and consider the use of a vasopressor infusion.

Significant muscle weakness can usually be avoided by the use of low concentrations of local anaesthetic drugs for postoperative analgesia (as opposed to that required for surgery). If significant motor block develops, consider reducing the infusion rate and / or concentration of local anaesthetic.

If the block is too high (e.g. involving arms), reduce the rate of infusion and / or the concentration of local anaesthetic. If respiratory muscle weakness occurs, ventilation may be necessary until the effects of the local anaesthetic wear off.

At the doses used, the addition of opioids to epidural infusion may significantly improve analgesia without significant increase in the side-effect profile. Nausea and itching may be helped by low-dose naloxone without loss of analgesia. CNS depression may require ventilation.

Analgesia produced by regional blockade may mask the pain associated with the onset of lower limb complications such as compartment syndrome following trauma or limb surgery. Check distal limbs regularly for evidence of infection, pressure injuries and compartment syndrome.

Epidural techniques carry a small but serious risk of epidural haematoma or abscess formation, which if unrecognized, can lead to spinal cord compression and paralysis. In routine practice this risk is very small. In ICU patients, however, the risk may be higher because of the effects of coagulopathy and sepsis. The magnitude of this risk is unquantifiable, although overall it remains very low.

Be sure to understand the difference between epidural and intrathecal catheters. An epidural catheter is placed in the ‘epidural space’. This is a potential space deep to the ligamentum flavum but outside the layers of the dura. An intrathecal catheter is placed through the dura and arachnoid mater, and lies within the subarachnoid space, i.e. in the cerebrospinal fluid. An intrathecal catheter may be used for CSF drainage and pressure monitoring following neurosurgery, spinal surgery or thoracic aortic aneurysm repairs, and occasionally for intrathecal drug administration (rarely, continuous spinal anaesthesia).

Problems in the immediate postoperative period may include the effects of prolonged surgery, massive fluid / blood loss, sepsis, tissue ischaemia / reperfusion, delayed recovery from anaesthesia and the effects of the stress response to surgery and trauma.

Anaesthesia and surgery may be prolonged because of the extensive nature of the procedure or because of technical complexity. Problems may include hypothermia, atelectasis, dehydration and fluid loss, anaesthetic drug accumulation, and the effects of pressure, including the development of compartment syndromes. This phenomenon has re-emerged recently following prolonged robotic surgery. (See Hypothermia, p. 224, and Peripheral compartment syndromes, p. 319.)

The causes of delayed recovery of consciousness following anaesthesia are often multifactorial. It may be impossible to determine initially which is the predominant problem. Factors that may contribute are shown in Box 14.3.

Most patients with delayed recovery of consciousness require a period of supportive care on ICU. A CT scan of the brain and EEG may be helpful to exclude significant intracranial pathology. In most cases the problem will resolve gradually over hours or days.

Muscle relaxants are used extensively in anaesthesia to facilitate tracheal intubation, provide relaxation for surgical procedures, and allow lighter planes of general anaesthesia. In the ICU, patients are usually left to clear muscle relaxants without use of reversal agents. Following anaesthesia, the recovery of neuromuscular function is often hastened by the use of anticholinesterase drugs (e.g. neostigmine). These increase the concentration of acetylcholine at the neuromuscular junction and reverse the effects of non-depolarizing neuromuscular blocking drugs (competitive antagonists at the acetylcholine receptor). They are used in combination with glycopyrrolate, which reduces the undesirable (muscarinic) effects of acetylcholine. Typical doses are:

neostigmine 2.5 mg + glycopyrrolate 0.5 mg.

Problems relating to residual neuromuscular blockade have become less common since the introduction of newer shorter-acting drugs such as atracurium. Occasionally, however, there may be delayed recovery of neuromuscular function. Factors that may contribute to this are shown in Box 14.4.

Patients with partial residual neuromuscular blockade typically exhibit jerky movements and make poor respiratory effort. Supra-maximal stimulation with a nerve stimulator may reveal fade on “train of four” confirming residual neuromuscular blockade. (See Monitoring neuromuscular blockade, p. 43.)

Give oxygen. Support ventilation if necessary.

If the patient has some neuromuscular function it may be appropriate to administer a first or second dose of reversal agent (usually neostigmine and glycopyrrolate) and then reassess the situation.

If this fails to improve the situation or if there is minimal neuromuscular function, the patient should be resedated, re-intubated and ventilated until return of neuromuscular function. Remember to explain to the patient what is happening. He or she may be paralysed, in pain and aware of the surroundings, but unable to communicate.

Hereditary cholinesterase deficiency (1:3000 population) is a specific cause of delayed recovery of neuromuscular function resulting from the delayed metabolism of suxamethonium (and mivacurium). Muscle function usually returns in 2–6 h. FFP can be given to replete cholinesterase and hasten the return of motor power, but is not usually necessary. Send blood to regional centre for identification of the particular pattern of cholinesterase deficiency. (See Suxamethonium, p. 43.)

This is common in the immediate postoperative period while patients are still in the recovery room and before full return of consciousness. This is usually transient, not severe, and readily managed by support of the chin, jaw thrust or the use of an artificial airway (e.g. oral or nasal airway).

More severe or prolonged cases, or those with associated respiratory depression, may require intubation and ventilation.

Following surgical procedures in the neck (e.g. thyroidectomy), postoperative bleeding into the tissues of the neck may occasionally produce airway obstruction by direct compression. In an emergency, you should open the surgical wound and decompress the bleeding to relieve pressure on the airway. The wound can then be formally explored by a surgeon in order to achieve haemostasis. If this fails to relieve the problem the patient will require intubation.

Patients with a fractured mandible frequently have their jaws wired together to ensure correct dental occlusion while the fracture heals. These patients should only be extubated once full consciousness and respiratory effort has returned. They are often admitted to intensive care in the immediate postoperative period for observation and monitoring. If airway obstruction occurs (e.g. due to vomiting), you should cut the wires to gain access to the airway and manage the situation as appropriate. (See Airway obstruction, p. 138.)

Postoperative respiratory insufficiency may be predictable in patients with pre-existing respiratory disease and this may be an indication for elective postoperative ventilation. In other patients it may arise for a number of reasons, and the problem is often multifactorial. Typical causes are shown in Box 14.5.

Many of these problems are resolved by a short period of ventilation in the ICU combined with simple corrective measures. (See also Respiratory failure, p. 118.)

Cardiovascular instability may arise due to pre-existing cardiovascular disease, from the predictable effects of the surgery, particularly when large fluid losses are expected, or as a result of untoward cardiovascular events. Typical causes are shown in Box 14.6. Many of these problems are solved by simple attention to details of fluid balance as the patient warms up after surgery. More difficult cases may require full invasive monitoring and cardiovascular support. (See Optimizing haemodynamic status, p. 78.)

Oliguria in the postoperative patient is often multifactorial, with cardiovascular instability, hypovolaemia and the stress response to surgery all contributing. This often improves with fluid loading as the patient rewarms and haemodynamic stability improves. (See Oliguria, p. 188, and Stress response to surgery and critical illness, p. 348.)

Following elective aortic aneurysm repair, patients can generally be allowed to warm up and are extubated after a few hours, as described above. Emergency aneurysm repairs may be more unstable and the management will depend upon individual circumstances.

Control of blood pressure is important. This should be maintained at a level which is normal for the patient to ensure adequate perfusion of vital organs, in particular the kidneys. At the same time significant hypertension should be controlled to prevent undue strain on both the myocardium and the vascular anastomosis. This may require use of nifedipine or GTN infusion, especially during the phase of emergence from sedation.

Renal dysfunction is common, particularly after suprarenal cross-clamping of the aorta. Spinal cord ischaemia and lower limb paralysis may also occur. Persistent ischaemia of the lower limbs despite optimization of haemodynamic status may require embolectomy or re-exploration of the graft. Persistent or worsening metabolic acidosis may indicate gut ischaemia. Seek surgical opinion.

The management of patients following free tissue transfer is similar to that described above. In addition, however, the adequate perfusion and survival of the graft is paramount.

The normal mechanisms that control blood flow in tissues are compromised in grafted tissue. The circulation to the graft is essentially passive and depends predominately on the flow through the feeding vessels. Aggressive fluid therapy should be used to maintain the patient’s circulating volume. This should be balanced, however, against the deleterious effects of increased oedema in the graft, caused by increased endothelial permeability resulting from reperfusion injury and the absence of lymphatic drainage. Fluid management is guided by CVP, urine output and core–peripheral temperature gradient. The usual response to any deterioration in these parameters should be to give further fluid.

At the same time the denervated vessels of the graft are highly sensitive to circulating catecholamines (endogenous or exogenous). Adequate analgesia is therefore essential. The patient should be kept as warm as possible and inotropes / vasopressor agents should be avoided except in extremis. Inodilators such as dopexamine may be of value in improving graft blood flow and survival. Seek advice.

If despite these measures graft perfusion appears impaired (dusky / congested / swollen), call the surgical team immediately. The vascular pedicles and vascular anastomoses may need surgical exploration.

Transplantation is a special case of free tissue transfer. The principles are similar to those described above, with particular management issues depending on the particular organ involved. Follow local protocols.

As soon as postoperative haemorrhage is suspected, inform the surgical team concerned. In severe cases, contact the senior surgeon involved direct to avoid delays that could compromise the safety of the patient.

The management of postoperative haemorrhage is essentially the same as any other form of haemorrhage. (See Major haemorrhage, p. 251.) The key issues are as follows:

Resuscitate and stabilize the patient, using an ABC approach.

Resuscitation strategy will depend upon circumstances, but ‘hypotensive resuscitation’ as practised in trauma may be beneficial in limiting the extent of the bleeding prior to achieving surgical haemostasis (see p. 309).

Initial resuscitation may be either with a crystalloid solution (such as Hartmann’s solution), colloid or blood where this is available.

Following a major surgical procedure blood will often be available in the intensive care blood fridge or transfusion laboratory. Failing that, the transfusion laboratory may be holding a ‘group and save’ sample which can be used for urgent cross-match. Otherwise you will need to send an urgent sample for cross-match.

Correct coagulopathy (see p. 258).

In some cases, postoperative bleeding is due to coagulopathy rather than failure of surgical haemostasis. Coagulopathy may result from derangement of clotting factors, and/or be exacerbated by the effects of acidosis, hypocalcaemia and hypothermia. Where possible, correct these factors prior to attempting surgical haemostasis.

The use of clotting products such as fresh frozen plasma, cryoprecipitate and platelets may be guided either by laboratory tests or point of care testing such as thromboelastography (see p. 259).

Seek advice on the use of antifibrinolytics, such as tranexamic acid or clotting factor concentrates such as prothrombin complex or activated factor V11a (see p. 261).

In many cases surgical exploration and haemostasis will be required. Therefore, good communication with both the haematology laboratory and the surgical and theatre team is required throughout. Do not forget to arrange for such devices as blood warmers, and in the case of massive haemorrhage, a rapid infusion device (such as the Level-1 infuser) or a cell saver if these are available.

The onset of symptoms may occur within 1–2 min of exposure to the precipitating agent or may be delayed up to 1–2 h and may be modified by the effects of general or regional anaesthesia. The clinical manifestations may include:

cutaneous flushing urticaria, angio-oedema

abdominal pain, nausea, vomiting and diarrhoea

laryngeal oedema, bronchospasm, increased airway pressure

acute pulmonary oedema

tachycardia, hypotension, cardiac arrest.

Life-saving treatment depends on early recognition and appropriate management. The differential diagnoses are given in Box 14.7.

Stop precipitating drugs.

Give oxygen. If airway compromised by facial oedema, laryngeal oedema or bronchospasm, secure airway by endotracheal intubation as soon as possible. Ventilate and commence external cardiac massage if necessary.

Establish i.v. access if not already done, and give rapid fluid load, e.g. 2–4 L crystalloid or colloid (remember that synthetic colloids may be the cause of the reaction!).

Give adrenaline (epinephrine) 0.5–1.0 mg i.m.

Establish arterial and central venous catheterization when appropriate.

Take blood (EDTA and serum) for later analysis.

Measure arterial blood gases. If significant acidosis consider 50–100 mmol sodium bicarbonate. (See Metabolic acidosis, p. 212.)

If persistent bronchospasm, give nebulized salbutamol 2.5–5 mg.

Glucocorticoids reduce late sequelae. Give hydrocortisone 200 mg i.m./i.v. followed by 50 mg 6-hourly.

Antihistamines are of no proven benefit but are often given. Consider chlorpheniramine (chlorphenamine) 10 mg i.m or i.v.

Following resuscitation, these patients should be managed in the ICU. Late reactions can result in clinical deterioration even some hours after initial stabilization. Cancel surgery and / or other interventional procedures unless life-saving. For further advice, see: http://www.aagbi.org/anaphylaxisdatabase.htm.

Following an anaphylactoid reaction, it is important to try and establish the cause so that future reactions may be avoided. Take a detailed history of this and other previous allergic reactions. Blood samples taken as soon after the reaction as possible and at regular intervals thereafter can be analysed for immune markers, including antibodies (IGE), complement and mediator levels. Mast cell tryptase peaks within 1–2 h of the event, so should be sampled within this time frame. A negative mast cell tryptase result does not rule out an anaphylactic reaction. Peri-event blood tests may help point toward a diagnosis of an anaphylactic reaction, but do not help identify the causative agent.

Radioallergosorbent tests (RAST) and interval skin-prick testing may determine the causative agent, but this is often inconclusive. Seek advice from laboratory services / immunology department.

It is essential that patients and their relatives are made aware of the reaction. In the case of nut allergy or bee sting anaphylaxis, patients are now given prefilled adrenaline (epinephrine) injectors for emergency use.

Discontinue trigger agents. Monitor ECG, SaO₂ and core temperature.

Intubate if not already.

Ventilate with 100% oxygen.

Monitor ETCO₂. Manage hypercarbia by hyperventilation.

Paralyse and ensure adequate sedation and analgesia.

Institute active cooling measures.

Give dantrolene 1 mg / kg i.v. over 10 min; repeat as necessary up to 10 mg / kg.

Monitor blood gases, potassium and calcium. Treat metabolic acidosis, hyperkalaemia and hypocalcaemia as appropriate.

Measure urine output and myoglobin. Give fluids and consider dopamine to maintain urine output. Mannitol and sodium bicarbonate increase the clearance of myoglobin. (Note: Dantrolene also contains mannitol to improve clearance of myoglobin).

Following stabilization, these patients must be monitored in the ICU. The half-life of dantrolene is approximately 5 h. Hyperpyrexia may recur, requiring further doses of dantrolene. Seek advice from national/regional MH centre. (See Hyperthermia, p. 224.)