Vasopressin Versus Vasopressin Analogues in Septic Shock

A 52 year old female was admitted to the ICU with septic shock secondary to cholangitis. She had liver cirrhosis secondary to alcoholic liver disease, although she had been abstinent since an admission with acute alcoholic hepatitis  2 years previously. She had recently entered the assessment pathway for orthotopic liver transplantation.

She presented to the Emergency Department with a short history of fever and confusion and falls. She was pyrexial, tachycardic and hypotensive. Her inflammatory markers were elevated and her liver enzyme profile suggested cholestasis. There were no other localising features on examination or preliminary investigation.

She was commenced in the ED on broad-spectrum antibiotic therapy (piperacillin-tazobactam) and fluid resuscitation consisting of Hartmann’s solution and 4% human albumin solution. Her blood pressure remained labile throughout the early part of her admission. She fulfilled the criteria for septic shock with evidence of evolving multi-organ dysfunction.


The patient received early, aggressive multi-organ support. Tracheal intubation and pressure-controlled ventilation were instituted due to grade III/ IV encephalopathy and a high work of breathing in response to profound metabolic acidaemia. A thorough clinical assessment of intravascular volume status was conducted, suggesting that the patient was adequately filled. Vasopressor therapy was initiated using noradrenaline to achieve a target MAP of 65mmHg. CVVHDF was commenced to control the severe acidaemia and hyperlactataemia.

The patient was vasoplegic and remained profoundly hypotensive despite rapidly escalating doses of noradrenaline and the addition of hydrocortisone. Continued assessment of intravascular status confirmed adequate filling and cardiac output monitoring using a pulse-contour analysis system confirmed a low SVRI- high cardiac output state.  Her noradrenaline requirements soon exceeded 0.4mcg/kg/min-1, at this point a vasopressin infusion was introduced at 0.03units/hr-1. This was associated with an improvement in haemodynamic indices; the target MAP was achieved and thereafter remained stable with a slow reduction in noradrenaline requirement. On day 2 the continuous vasopressin infusion was converted to terlipressin by bolus dose regime (2mg QDS).

An urgent ultrasound scan of her biliary system revealed an obstructed common bile duct which was treated by percutaneous biliary drainage. An Enterococcus was isolated from drain fluid and blood cultures within 48 hours and antibiotic therapy tailored accordingly. The patient was weaned from organ support and discharged to the hepatology unit 9 days after admission.

What is the rationale for the use of vasopressin in septic shock? Are vasopressin analogues as effective?Read More »


Extracorporeal CO2 removal

A 42 year old man presented with a week-long history of increasing shortness of breath, cough  (productive of purulent sputum) and fevers on a background of significant chronic lung disease. He had a ten year history of interstitial lung disease and was on the waiting list for a lung transplant. He used oxygen at a rate of 2 litres per minute at home, 24 hours a day. His usual exercise tolerance of 200 metres had been significantly reduced for the past week. His regular medications included seretide and salbutamol inhalers, lansoprazole, azathioprine, prednisolone alendronate.

On arrival in hospital, he was alert and orientated. He had a patent airway, but was tachypnoeic (rate of 50/minute) using his respiratory accessory muscles and a tracheal tug was evident. An arterial blood gas revealed type two respiratory failure (pH 7.26; pO2 8.14, pCO2 7.52 on 15 liters/min of face mask oxygen). He was hypotensive (80/40mmHg) and tachycardic (130/minute, sinus rhythm). A pyrexia of 39.2°C was recorded. Blood results showed normal renal function, a slightly elevated white cell count of 14.

The patient was admitted to the high dependency for close monitoring in view of his history and presentation. He was commenced on treatment for a presumed infection (viral or bacterial) with oseltamivir, co-amoxiclav and clarithromycin and given three “pulsed” doses (750mg) of methylprednisolone. He remained stable for the next twelve hours.

Early the next morning, he became very hypoxic (oxygen saturations less than 50%), bradycardic (<35 beats per minute) and had a brief hypoxic respiratory arrest. He received 1 cycle of cardiopulmonary resuscitation and was intubated. There was subsequently a return of spontaneous circulation.

The next 24 hours involved a period of difficulty with ventilation. His peak airway pressures were very high, despite being paralysed and a low volume/high respiratory rate strategy being employed. He was discussed with a tertiary respiratory centre and it was decided that he should be transferred for insertion of a pumpless arteriovenous interventional lung assist (for extracorporeal carbon dioxide removal) as a bridge prior to lung transplantation. He had formal ultrasound measurement of his femoral arteries. His left common femoral artery was widely patent (AP and transverse diameter of 8-9mm throughout), but the right was only 4-5mm throughout.

In the meantime, his peak airway pressures were consistently between 35 and 40cmH2O, despite tidal volumes of 230ml, 3.8ml/kg). With a rate of 32-35 breaths per minute, his pH was  initially maintained above 7.2, with a pCO2 of 9-11kPa. Over the course of the next few hours, this became increasingly difficult to achieve. His oxygen requirements did not escalate (an FiO2 of 0.6 provided a pO2 of 8-9kPa). When his pCO2 increased to 15.4kPa and his pH dropped to 7.17, further adjustments were made and the PEEP decreased to 5cmH2O from 10cmH2O. His noradrenaline requirements were increasing and with the aid of the cardiac output monitoring, he was cautiously given fluid with a good response.

He was transferred to the centre in which a lung transplant could be performed within hours of the referral. A Novalung device was inserted and he underwent a bilateral lobar lung transplant several days later. He was in hospital for 6 weeks and made a very good long-term recovery. At six months, he was extremely well and was undertaking his activities of daily living completely normally with stable lung function. He even managed to complete an eight mile bike ride.

What is the rationale for extracorporeal lung assist?
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Mechanical Ventilation of Chronic Obstructive Airways Disease

A 68-year-old went into respiratory arrest on the chest ward. He had been admitted 2 weeks previously for an exacerbation of chronic obstructive airways disease (COAD). He has had two previous episodes of reduced conscious level due to hypercapnoea, which resolved with non-invasive ventilation and oxygen titration.

He was immediately intubated on the ward and transferred to the intensive care unit for ventilation. Hypoxia was corrected to a PaO2 >8.0kPa with a moderate FiO2. However he remained very difficult to ventilate and maintained a persistently high PaCO2. The highest level was 21kPa. He was treated with B2 agonist nebulisers, anti-muscarinic nebulisers, systemic steroids, aminophylline infusions, magnesium infusions and a ketamine infusion. He also needed vasopressor support and for a period of time continuous renal replacement therapy. After a week when his ventilator pressures reduced he had an uneventful percutaneous tracheostomy. Sedation was then reduced and he was awake and spontaneously breathing but with a high level of support. He was recurrently troubled by episodes of bronchospasm and air trapping. The lowest settings for inspiratory pressure were 14 cmH2O. He deteriorated a number of times before care was withdrawn and he died 20 days later.

Can we predict which COAD patients will benefit from mechanical ventilation?

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Pneumococcal Sepsis

An elderly man with a background of ischaemic heart disease, severe aortic stenosis and type 2 diabetes mellitus presented following recent travel from Hong Kong with shortness of breath and hypoxia. A chest X-ray confirmed left lower lobe consolidation (CRP 502, WCC 22) and he was commenced on broad spectrum antibiotics (Tazocin and Clarithromycin). Over the following 12 hours he deteriorated on the ward, with worsening hypoxia, hypotension and anuria.

He required emergency admission to intensive care for intubation and ventilation, and required inotropic support. He developed a severe metabolic acidosis and rising lactate, for which  haemofiltration was commenced. Vasopressin was added, followed by dobutamine, and hydrocortisone started for inotrope resistant hypotension. He remained ventilated on 100% oxygen, with high pressure support. He had a positive pneumococcal antigen, and high dose benzylpenicillin was added to his antibiotic regime, along with Oseltamivir (Tamiflu). Despite 12 hours of intensive therapy his acidosis worsened and he failed to respond to increasing doses of inotropic support, dying 30 hours after presentation to hospital.

What are the clinical features of pneumococcal sepsis?Read More »

Attempted Suicide and Treatment Withdrawal

A elderly man  was found unconscious at home having taken an overdose of prescription medication. This event may have been precipitated by a recent bereavement and worsening of his preexisting depression for which he had recently been reviewed by psychiatric services and commenced on an SNRI. He left a note at the scene of the suicide attempt, clearly stating that he intended to take his own life and did not wish to be resuscitated in the event of being found alive. He was discovered in his home by a relative who had been growing increasingly concerned as to his welfare, having not spoken to him for several days. On arrival in ED his Glasgow coma score (GCS) was 3/15. He was known to be taking venlafaxine for depression and amitriptyline for chronic back pain, and empty packets of each drug were found at his home.

He was intubated and transferred to the intensive care unit. Supportive care was provided including vasopressors (noradrenaline) for hypotension, electrolyte correction and ventilatory support. Plain chest radiograph showed a probable aspiration pneumonitis affecting the right upper and middle lobe. He was hypoxic with a high Fi 02 requirement and needed high levels of PEEP to maintain adequate oxygenation. His conscious level fluctuated over several days and he became increasingly agitated and exhibited signs of distress. At this stage it was not clear if he was orientated in time, place or person. He underwent percutaneous tracheostomy to facilitate weaning and reduce sedation requirements.

We were then able to wean him from sedation by day 11 of his admission. The patient’s ventilatory requirements were still high requiring mean airway pressures of 30 cmH2O, PEEP of 10 cmH2O, and an inspired oxygen concentration of 60%. At this stage he indicated to the ITU team that he did not wish treatment to be continued. We found him to be fully orientated in terms of time and place and he was aware of the preceding events and his intentional overdose. It was clearly explained to him that if treatment were discontinued he would die. He indicated to us that he had no intention of changing his mind.

We referred him to the liaison psychiatrist for the hospital who independently assessed and found him to be competent and able to fully understand the implications of such a decision, i.e. his likely death from respiratory failure. The psychiatrist also found him to be depressed but noted that this did not interfere with his competence and ability to give or withhold his consent. With his consent, his family were informed of this development. They had been agonizing for some time over whether they had made the right decision to call emergency services when they first found him. They attempted to dissuade him but his resolve was unshakeable. Invasive ventilation was withdrawn on the morning of his 15th day of ITU as per his wishes. Diamorphine was administered to reduce symptoms of respiratory distress. He died of hypoxia later that day. Cause of death was recorded as aspiration pneumonia.

Describe the ethical and legal framework utilised in the management of this patient.Read More »

Management of Variceal Haemorrhage

A 60-year-old alcoholic was admitted with large-volume, frank haematemesis. On presentation he was hypotensive, tachycardic and obtunded with multiple stigmata of chronic liver disease including a moderate volume of ascites and palpable splenomegaly. Initial phlebotomy revealed a haemoglobin of 6.4 g/dL, INR of 4.5 and bilirubin of 54 μmol/L. Arterial blood gas analysis demonstrated a significant metabolic acidosis and lactate of 11 mmol/L. Large bore intravenous access was established and administration of crystalloid initiated, targeting a systolic blood pressure of 90 mmHg. Urgent cross-match of 10 units of packed red blood cells, clotting products and platelets was requested and the patient was transferred to theatre where upper gastrointestinal tract endoscopy was performed under general anaesthesia. This demonstrated three columns of varices involving the gastro-oesophageal junction. Attempts at banding and injection of sclerosant met with variable success. A Senstaken-Blakemore tube was inserted due to incomplete haemostasis and further attempts at endoscopic therapy abandoned.

The patient was transferred to intensive care. Intravenous cefotaxime and terlipressin were commenced. Further transfusion of clotting products continued as guided by thromboelastography with some slowing of transfusion but red cell requirements persisted at a rate of 1-2 units of blood per hour. At 12 hours, repeat endoscopy was performed – further attempts at sclerotherapy were unsuccessful and transjugular intrahepatic porto-systemic shunting was performed by the interventional radiology team. Upon return to intensive care, a significant reduction in bleeding was noted and both haemodynamic indices and coagulopathy improved over the following 12 hours. A repeat endoscopy demonstrated no evidence of active ongoing bleeding. At this point sedation was stopped; some encephalopathy was evident although this improved in the following 24 hours. Extubation occurred on day 3 after admission and he was discharged to the high-dependency unit at day 5 without significant ongoing acute issues.

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Obesity Hypoventilation Syndrome

Obesity Hypoventilation Syndrome

 A 66 year old man was brought by ambulance to ED after becoming acutely dyspnoeic at home, and his wife had struggled to wake him after an afternoon sleep. He had a moderate smoking history of 20 pack years and quit 20 years ago, and drank approximately 20 units of alcohol as beer per week. There were no preceding prodromal respiratory or infective symptoms reported. On examination, he was obese with a weight of 120 kg. He was snoring, which eased with a chin-lift or jaw thrust, but he would not tolerate an airway adjunct. His respiratory rate was 8 and shallow, producing SpO2 84% on high flow oxygen. He was flushed and veno-dilated peripherally, with a tachycardia of 110 bpm sinus rhythm. Most notably, he was difficult to rouse, with a GCS of 9 (E2 M5 V2). Arterial blood sampling revealed a profound hypercapnoeic respiratory acidosis with no degree of compensation. Chest X-ray showed poorly expanded lungs with bilateral basal atelectasis and prominent pulmonary vasculature. Empiric naloxone was ineffective and he was commenced on non-invasive ventilation (NIV). The working diagnosis was an acute non-infective exacerbation of previously undiagnosed chronic obstructive pulmonary disease (COPD). Treatment involved bronchodilators, steroids and bilevel pressure support non- invasive ventilation.
One hour after NIV had been established, the patient’s respiratory acidosis was worse and his clinical picture was unchanged. He was intubated then transferred to Intensive Care. CTPA ruled out significant pulmonary emboli but was suggestive of pulmonary hypertension. Ventilation was not difficult, with near normal inspiratory pressures, and his minimal wheeze resolved quickly. As his respiratory acidosis normalised, his GCS rapidly improved to the point of safe extubation after just 48 hours. Given his obesity he was extubated to non-invasive pressure support ventilation immediately. After a further 24 hours, his gas exchange began to deteriorate again. Increasing inspiratory pressure improved his tidal volumes but his intrinsic rate of breathing slowed such that his minute ventilation remained static. He eventually found a stable equilibrium using nocturnal bilevel pressure support with a high mandatory backup rate (pressure control), which maintained a normal minute ventilation. Although he developed hypercapnoea each night, this was mild and eventually compensated. With the NIV, he did not obstruct, have hypopnoeic events or desaturated overnight, which markedly improved his daytime somnolence and effort of breathing.

What are the clinical features and approaches to management of obesity hypoventilation syndrome?

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Transfusion in Sepsis

Transfusion in Sepsis

A 85 year old man presented with acute bowel obstruction. He had a history of hypertension and diverticulitis disease, but was active for his age. He was not known to have coronary or any other vascular pathology. At laparotomy, a large diverticulitis abscess was identified. When this was manipulated, he developed an SVT with a ventricular rate of 210 bpm which progressed to VT. He received 1 mg adrenaline and 2 minutes CPR in total, with no electrical shocks. At this point perfusion and pressure returned. Surgery was expedited and simplified. He remained intubated and ventilated on ITU post-operatively. ECG demonstrated global t-wave inversion. He required noradrenaline and adrenaline to maintain blood pressure. During the initial 48 hours, his haemoglobin (Hb) fell from 11.9 g/dl to 8.1 g/dl, raising the suggestion of packed red cell (PRC) transfusion.

What is the most appropriate threshold to transfuse packed red cells in critically ill patients?Read More »

ICU Admission with Haematological Malignancy

Outcomes of ICU Admission with Haematological Malignancy

An middle aged woman presented with a blast crisis following acute transformation of preexisting chronic myelomonocytic leukaemia. She failed to respond to several cycles of chemotherapy and underwent allogeneic bone marrow transplant. She subsequently developed neutropaenic septic shock and was found to have fungal pulmonary abscesses. Her sepsis was aggressively managed on ICU and she made steady progress and eventually recovered, and was discharged from hospital 5 weeks after her ICU admission.

What is the current evidence related to the mortality and morbidity associated with admission to intensive care for patients with haematological malignancy?Read More »

Mechanical Ventilation in patients with COPD

Predicting Outcomes of Mechanical Ventilation in patients with COPD

An elderly man with an infective exacerbation of COPD deteriorated during his medical admission with type 2 respiratory failure. He was commenced on ward-based non-invasive ventilation while establishing further history. He was on home nebulisers, was awaiting assessment for home oxygen, and was limited to household mobility only. He could not climb stairs. He had secondary polycythaemia. After discussion with the patient and family, a ward-based ceiling of care was set. He remained on NIV for several days before being weaned off and discharged to a rehabilitation facility after a two week admission.

Can we predict outcomes for patients with respiratory failure and COPD who require invasive ventilation?Read More »