Abstract
Purpose: Hyperthermic intra-thoracic chemotherapy (HITOC) combined with cytoreductive surgery (CRS) is a novel approach in the management of pseuodmyxoma peritonei with thoracic extension. The haemodynamic effects of hyperthermic chemotherapy present an anaesthetic challenge. Here, we describe the haemodynamic changes seen during HITOC.
Materials and methods: A retrospective case note review of adult patients undergoing CRS with HITOC from 2009 to 2016. Intra-operative haemodynamics were measured using the LIDCOrapidTM brand of invasive cardiac output (CO) monitor. Intravenous fluids, vasopressor requirements and urine output (UO) were recorded.
Results: Four patients were included in the study. Mean heart rate (HR) peaked at 20 min following commencement of HITOC. The difference between HR at time 0 and at peak was minimal. There was minimal change in CO, and stroke volume variation (SVV) remained stable. Vasopressor dose was minimally changed throughout surgery. Average UO during HITOC was 142.5 ± 109.6 mls at 60 min. Mean fluid requirements during HITOC was 586.2 ± 441.2 mls. No significant change occurred in pH or base excess (BE).
Conclusions: Significant haemodynamic instability including cardiac asystole has been reported during HITOC. The application of hyperthermic agents to the thorax results in vasodilatation, cardiac warming and compression of mediastinal vessels. Measurement of haemodynamic variables allowed careful titration of intravenous fluid therapy to CO and stroke volume, allowing for haemodynamic stability. This has not been described elsewhere.
Introduction
Hyperthermic intra-thoracic chemotherapy (HITOC) combined with cytoreductive surgery (CS) is a novel approach in the management of malignant pleural disease [Citation1]. It is applied intra-operatively at the time of surgical resection of pleural surface tumours and results in acute physiological derangement that is challenging to manage [Citation2]. The application of hyperthermic chemotherapy agents to the thorax results in a significant increase in core temperature with an associated systemic inflammatory response. Tachycardia, hypotension and cardiac arrest have been reported at the time of therapy [Citation3].
Pseudomyxoma peritonei (PMP) is a condition characterised by the production of mucinous ascites within the abdomen [Citation4]. Thoracic extension of this tumour is extremely rare [Citation5] and requires thoracic surgical intervention. PMP is a unique subset of pleural surface malignancy due to the pathophysiology of this condition. Surgical resection of this mucinous tumour requires extensive use of high-powered diathermy, which can result in physiological changes akin to those following a major burn. These patients may be hypoalbuminaemic as a result of malnutrition and the large volume of mucous produced. PMP patients therefore require unique intra-operative management strategies, particularly with regard to management of volume status. Appropriate intravenous volume therapy guided by invasive cardiac output (CO) monitors has been shown to be valuable in preventing the haemodynamic changes seen in PMP patients receiving intra-peritoneal hyperthermic chemotherapy for abdominal disease [Citation6].
Given the severe haemodynamic changes seen in previous reports [Citation3], we describe the use of an invasive CO monitor to guide management of volume status and haemodynamic parameters during the HITOC phase of surgery for these patients.
Materials and methods
Patients who underwent cytoreductive thoracic surgery with HITOC between February 2009 and February 2016 were included in this retrospective review. All patients had thoracic spread of a primary appendix tumour with pseudomyxoma peritoneii. No patients were excluded from the study.
After institution of AAGBI standard monitoring, anaesthesia was induced intravenously with fentanyl 1–2 mcg/kg, propofol 2–4 mg/kg and an intubating dose of muscle relaxant. A double lumen Robertshaw endotracheal tube was inserted and position confirmed using fibre optic bronchoscopy. Following this an arterial line, further venous access, a urinary catheter and oesophageal temperature probe were inserted. Patients received thoracic epidural anaesthesia, intercostal blocks or intravenous opiate analgesia. Intravenous fluid therapy was goal-directed using a LIDCOrapid™ brand invasive CO monitor; fluid boluses were titrated to maintain a stroke volume variation (SVV) of less than 10%. Anaesthesia was maintained with a volatile agent and remifentanil infusion at 0.1–0.2 mcg/kg/min. To counteract the vasodilation produced by volatile agents, opiate infusion and epidural anaesthesia, a phenylephrine infusion was commenced at 0–0.9 mcg/kg/min, to achieve a mean arterial pressure (MAP) of 60–75 mmHg. Where phenylephrine requirements were high, noradrenaline infusion (0.02–0.1 mcg/kg/min) was commenced in its place. Patients were placed in the lateral position for surgery with a forced air warming blanket to prevent hypothermia during the surgical resection phase. Active warming was discontinued prior to commencing the HITOC phase of the procedure.
HITOC was commenced immediately following the completion of surgical resection of tumour. Patients underwent pleurectomy with decortication, where required. The chest cavity was filled with mitomycin C 10 mg/m2 diluted in 3–5 L of fluid at 42 °C for 30–60 min. One-lung ventilation was commenced once positioned on the operating table and continued until after the HITOC phase was completed, when the lung was reinflated and wound was closed. Surgical access was either thorascopic with two structured ports and one 5 cm utility port, or with thoracotomy. Patients received volume-controlled positive pressure ventilation with positive end expiratory pressure (PEEP) of 5–8 cm H2O).
During HITOC and for 30 min following it, data were collected on oesophageal temperature, heart rate (HR), MAP, central venous pressure (CVP), CO, systemic vascular resistance (SVR), SVV, urine output (UO), arterial pH, base excess (BE) and arterial lactate concentration. Intravenous fluids administered and dose of vasopressor administered were also recorded. Haemodynamic parameters were recorded every 10 min and arterial blood gases, intravenous fluids administered and UO were recorded every 30 min. Data were analysed using Microsoft Excel. Mean and standard deviation values were calculated.
Results
Four patients were included in the study. Mean age was 53 years (range 43–70) with three females and one male. Mean body weight was 65 kg (range 58–82). All patients had pseudomyxoma of appendiceal origin with thoracic spread. All patients had undergone laparotomy to resect abdominal disease in the previous 5 years. Thoracic surgery with HITOC was performed more than 1 year following laparotomy in all patients. Average time to commencing chemotherapy was 292 min (range 210–360) and average total length of surgery was 386 min. One patient received 20 mg of frusemide prior to commencement of chemotherapy. Two patients received 30 min of HITOC and two patients received 60 min of HITOC, depending on clinical need. Data were collected for 60 min from commencing HITOC in all patients. shows measurements taken during HITOC.
Table 1. Measurements taken during HITOC.
Oesophageal temperature increased from a mean of 36.95 °C–38 °C at 60 min. Mean HR was peaked at 20 min following the commencement of HITOC. The difference between HR at time 0 and at peak was minimal (). There was minimal change in CO (), and SVV () remained stable. Phenylephrine or noradrenaline dose was unchanged throughout the HITOC phase, except in one patient where the dose of phenylephrine increased by 400 mcg/h after 20 min of HITOC. MAP changes are displayed in . One patient received noradrenaline 0.2 mcg/kg/min throughout surgery, one patient had no vasopressor requirement. displays the vasopressor requirements for each patient during HITOC.
Figure 1. HR changes during HITOC.
Figure 2. CO changes during HITOC.
Figure 3. SVV changes during HITOC.
Figure 4. MAP changes during HITOC.
Figure 5. Dose of vasopressor required during HITOC. All patients who required vasopressors received phenylephrine, except for patient 1 who received noradrenaline. All patients who required vasopressors received phenylephrine, except for patient 1 who received noradrenaline.
Average UO during HITOC was 110.8 ± 78.4 mls at 30 min and 142.5 ± 109.6 mls at 60 min. Mean fluid requirement during HITOC was 586.2 ± 441.2 mls. Average blood loss during surgery was 1087.5 ± 1742 mls. Two patients each received 2 units of blood, and one of these received 2 units of cryoprecipitate. No other blood products were transfused intra-operatively. There was no significant change in pH or BE in any of the patients over the studied period. No patients suffered peri-operative renal injury. Mean length of stay was 12 days. Mortality at 1 year was zero.
Discussion
Thoracic CS combined with HITOC is an evolving surgical technique [Citation4]. Hyperthermic chemotherapy agents penetrate tumour cells more effectively and result in an increased cytotoxicity effect [Citation7], but have been associated with severe haemodynamic effects. Here, we describe relative haemodynamic stability during and immediately following the HITOC phase of surgery. This is in contrast to other published data on the subject where considerable haemodynamic instability with hypotension, tachycardia increased vasopressor requirements and an episode of asystole [Citation3,Citation8] were reported in one series. In our series, the use of goal-directed fluid administration, with fluid boluses titrated to SVV, using CO monitoring allowed haemodynamic parameters to remain remarkably stable without large increases in vasopressor support requirements. Goal-directed fluid therapy has been shown to reduce cardiovascular complications of surgery [Citation9]. A series of eight patients with mesothelioma or lung adenocarcinoma who underwent cisplatin HITOC reports no intraoperative complications, although there is no specific mention of changes in haemodynamic parameters, these patients underwent pre-operative intravenous fluid therapy to ensure adequate volume status prior to surgery [Citation10]. The series reports one case of post-operative renal toxicity.
There are multiple causes for the potential haemodynamic instability that can result during HITOC. Heat energy will be absorbed leading to an increase in core body temperature. This causes vasodilatation and an increased CO state. The proximity of the chemotherapy solution to the mediastinal structures may have additional adverse effects. HITOC has a target temperature of 42 °C. This temperature will be directly transmitted to the mediastinal structures causing cardiac warming. There is also the potential for compression of the mediastinal vessels affecting venous return. Adequate intravascular filling will reduce compression of mediastinal vessels, improve CO, decrease SVV and reduce vasopressor requirements. Over transfusion of fluids, however, has inherent risks including pulmonary oedema.
We used a CO monitor for haemodynamic measurements during the hyperthermic phase of surgery, to our knowledge this has not been described elsewhere. Measurement of haemodynamic variables allowed careful titration of intravenous fluid therapy to CO and stroke volume, allowing for improved stability. We have described previously how CO monitoring allows accurate control of haemodynamic parameters during the hyperthermic phase of abdominal surgery to resect intraperitoneal PMP disease [Citation6] and this data support the use of CO monitoring for intraoperative hyperthermic chemotherapy.
This is a small series of patients, and this reflects the rare nature of thoracic extension of PMP tumours. This condition is amenable to surgical resection with good 5 year survival rates [Citation10] but a single centre is unlikely to gain a significant caseload in the management of these patients. Anaesthesia for HITOC is challenging and potentially unstable and this data adds to the worldwide knowledge base on the optimal management strategy.
The peri-operative management of this patient group is complex. Ensuring an adequate preload must be balanced against the risks of pulmonary oedema and lung injury resulting from excessive fluid administration [Citation11]. Thoracic complications following intraperitoneal CS and hyperthermic intraperitoneal chemotherapy are relatively common [Citation12]. Reported complications include ateletasis, infection, pleural effusions, pulmonary oedema and pulmonary interstitial pneumonitis [Citation11–14]. There is the potential for these risks to occur following HITOC. Additionally, hyperthermic intra-cavity chemotherapy is associated with a risk of renal injury. Studies suggest that some degree of acute kidney injury (AKI) is present in between 5–30% of patients who have hyperthermic intraperitoneal chemotherapy [Citation15]. Methods to reduce the incidence of AKI include maintenance of normovolaemia, and forced diuresis. There are risks therefore of both inadequate and excessive fluid administration. We suggest that CO monitoring with goal-directed fluid administration could reduce the incidence of intraoperative haemodynamic complications in patients having HITOC procedures.
Conclusions
CO monitoring and goal-directed fluid therapy allows the maintenance of normovolaemia in patients undergoing thoracic CS combined with HITOC. This allows patients receiving HITOC to remain haemodynamically stable. Fluid and vasopressor administration during the HITOC phase can be safely guided using information from the CO monitor.
Disclosure statement
The authors report no declarations of interest.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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